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Endocrine

Glands

Lightmicrograph of a pancreaticislet showing

insulin-secreting beta cells(green) and the

glucagon-secreting cells(red).

Part 3 Integration and ControlSystems

Homeostasisdepends on the precise

regulation of the organs and organ

systemsof the body. Together the nerv-

ousand endocrine systems regulate and

coordinate the activityof nearly all other

body structures. When either the nervous

or endocrine system failsto function properly,

conditionscan rapidly deviate from homeostasis.

Disordersof the endocrine system can result in dis-

easeslike insulin-dependentdiabetes and Addison’s disease. Early in the 1900s,

people who developed these diseasesdied. No effective treatments were avail-

able for these and other diseasesof the endocrine system, such as diabetes in-

sipidus, Cushing’ssyndrome, and many reproductive abnormalities. Advances

have been made in understanding the endocrine system, so the outlookfor peo-

ple with these and other endocrine diseaseshas improved.

The endocrine system issmall compared to its importance to healthybody

functions. It consistsof several small glands distributed throughout the body

thatcould escape notice if not for the importance of the small amounts of hor-

monesthey secrete.

Thischapter ﬁrst explains the functions of the endocrine system (598) and

then proﬁlesthe pituitary gland and hypothalamus (598), hormones of the pitu-

itarygland (601), thyroid gland (607), parathyroid glands (613), adrenal glands

(615), and pancreas(620). It then moves to discussions about hormonal regula-

tion of nutrients(624), hormones of the reproductive system(627), pineal body

(628), thymus (630), and gastrointestinal tract (630), and hormonelike sub-

stances(630). The chapter concludeswith a look at the effects of aging on the en-

docrine system(632).

CHAPTER

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Functions of the Endocrine

System

Objective

■ Describe the main regulatory functions of the endocrine

system.

Several pieces ofinformation are needed to understand how

the endocrine system regulates body functions.

1. the anatomy ofeach gland and its location;

2. the hormone secreted by each gland;

3. the target tissues and the response oftarget tissues to each

hormone;

4. the means by which the secretion ofeach hormone is

regulated;

5. the consequences and causes,if known, of hypersecretion

and hyposecretion ofthe hormone.

The main regulatory functions of the endocrine system

include:

1. Metabolism and tissue maturation.The endocrine system

regulates the rate ofmetabolism and inﬂuences the

maturation oftissues such as those of the nervous

system.

2. Ion regulation.The endocrine system helps regulate blood

pH as well as Na

,and Ca

concentrations in the

blood.

3. Water balance.The endocrine system regulates water

balance by controlling the solute concentration ofthe

blood.

4. Immune system regulation.The endocrine system helps

control the production ofimmune cells.

5. Heart rate and blood pressure regulation.The endocrine

system helps regulate the heart rate and blood pressure and

helps prepare the body for physical activity.

6. Control ofblood glucose and other nutrie nts.The endocrine

system regulates blood glucose levels and other nutrient

levels in the blood.

7. Control ofreproductive functions. The endocrine system

controls the development and functions ofthe reproductive

systems in males and females.

8. Uterine contractions and milk release.The endocrine system

regulates uterine contractions during delivery and

stimulates milk release from the breasts in lactating

females.

1. What pieces of information are needed to understand how

the endocrine system regulatesbody functions?

2. List 8 regulatory functions of the endocrine system.

Part3 Integration and ControlSystems598

Pituitary Gland and

Hypothalamus

Objectives

■ Describe the embryonic development, anatomy, and location

of the pituitarygland as well as the structural relationship

between the hypothalamusand the pituitary gland.

■ Describe the means by which anterior pituitary hormone

secretion isregulated, and list the major releasing and

inhibiting hormonesreleased from hypothalamic neurons.

■ Describe the secretory cells of the posterior pituitary,

including the location of theircell bodies, and the sites of

hormone synthesis, transport, and secretion.

The pituitary (pi-tooi-ta¯r-re¯) gland, or hypophysis (hı¯-

pofi-sis;an undergrowth), secretes nine major hormones that reg-

ulate numerous body functions and the secretory activity ofseveral

other endocrine glands.

The hypothalamus (hı¯po¯-thala˘-mu˘s) ofthe brain and the

pituitary gland are major sites where the nervous and endocrine sys-

tems interact (ﬁgure 18.1).The hypothalamus regulates the secre-

tory activity of the pituitary gland. Indeed,the posterior pituitar y is

an extension of the hypothalamus. Hormones, sensory informa-

tion that enters the central nervous system,and emotions, in turn,

inﬂuence the activity ofthe hypothalamus.

Structure ofthe Pituitary Gland

The pituitary gland is roughly 1 cm in diameter,weighs 0.5–1.0 g,

and rests in the sella turcica ofthe sphenoid bone (see ﬁgure 18.1).

It is located inferior to the hypothalamus and is connected to it by

a stalk oftissue called the infundibulum (in-fu˘n-dibu¯-lu˘m).

The pituitary gland is divided functionally into two parts:the

posterior pituitary,or neurohypophysis (nooro¯-hı¯-pofi-sis),and

theanterior pituitary, or adenohypophysis (ade˘-no¯-hı¯-pofi-sis).

PosteriorPituitary, or Neurohypophysis

The posterior pituitary is called the neurohypophysis because it is

continuous with the brain (neuro-refers to the nervous system). It

is formed during embryonic development from an outgrowth of

the inferior part of the brain in the area of the hypothalamus (see

chapter 29).The outgrowth of the brain forms the infundibulum,

and the distal end ofthe infundibulum enlarges to form the poste-

rior pituitary (ﬁgure 18.2).Secretions of the posterior pituitary are

considered neurohormones (noor-o¯ho¯rmo¯nz) because it is an

extension ofthe nervous system.

AnteriorPituitary, or Adenohypophysis

The anterior pituitary,or adenohypophysis (adeno- means gland),

arises as an outpocketing of the roof of the embryonic oral cavity

called the pituitary diverticulum or Rathke’s pouch,which grows

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Chapter 18 Endocrine Glands 599

toward the posterior pituitary.As it nears the posterior pituitary,

the pituitary diverticulum loses its connection with the oral cavity

and becomes the anterior pituitary.The anterior pituitary is sub-

divided into three areas with indistinct boundaries: the pars

tuberalis, the pars distalis, and the pars intermedia (see ﬁgure

18.2).The hormones secreted from the anterior pituitary, in con-

trast to those from the posterior pituitary,are not neurohormones

because the anterior pituitary is derived from epithelial tissue of

the embryonic oral cavity and not from neural tissue.

Relationship ofthe Pituitary to the Brain

Portal vessels are blood vessels that begin and end in a capillary

network. The hypothalamohypophysial (hı¯po¯-thala˘-mo¯-

hı¯po¯-ﬁze¯-a˘l)por tal system extends from a part of the hypothal-

amus to the anterior pituitary (ﬁgure 18.3).The primary capillar y

network in the hypothalamus is supplied with blood from arteries

that deliver blood to the hypothalamus.From the primary capil-

lary network, the hypothalamohypophysial portal vessels carry

blood to a secondary capillary network in the anterior pituitary.

Veins from the secondary capillary network eventually merge with

the general circulation.

Neurohormones, produced and secreted by neurons ofthe

hypothalamus,enter the primary capillary network and are carried

to the secondary capillary network.There the neurohormones leave

the blood and act on cells ofthe anterior pituitary. They act either as

releasing hormones, increasing the secretion of anterior pituitary

hormones,or as inhibiting hormones, decreasing the secretion of

anterior pituitary hormones. Each releasing hormone stimulates

and each inhibiting hormone inhibits the production and secretion

of a speciﬁc hormone by the anterior pituitary.In response to the

releasing hormones,anterior pituitar y cells secrete hormones that

enter the secondary capillary network and are carried by the general

circulation to their target tissues. Thus, the hypothalamohy-

pophysial portal system provides a means by which the hypothala-

mus, using neurohormones as chemical signals, regulates the

secretory activity ofthe anter ior pituitary (see ﬁgure 18.3).

Several major releasing and inhibiting hormones are released

from hypothalamic neurons. Growth hormone-releasing hor-

mone (GHRH) is a small peptide that stimulates the secretion of

growth hormone from the anterior pituitary gland, and growth

hormone-inhibiting hormone (GHIH), also called somato-

statin, is a small peptide that inhibits growth hormone secretion.

Thyroid-releasing hormone (TRH)is a small peptide that stimu-

lates the secretion ofthyroid-stimulating hormone from the ante-

rior pituitary gland. Corticotropin-releasing hormone (CRH) is

a peptide that stimulates adrenocorticotropic hormone from the

anterior pituitary gland. Gonadotropin-releasing hormone

(GnRH)is a small peptide that stimulates luteinizing hormone and

follicle-stimulating hormone from the anterior pituitary gland.

Prolactin-releasing hormone (PRH) and prolactin-inhibiting

hormone (PIH) regulate the secretion of prolactin from the

Third

ventricle

Hypothalamus

Optic

chiasm

Pituitary

gland

Mammillary

body

Infundibulum

Sella turcica

of sphenoid

bone

Figure 18.1

The Hypothalamusand Pituitary Gland

A midsagittalsection of the head through the pituitary gland showing the

location ofthe hypothalamus and the pituitary. The pituitarygland is in a

depression called the sella turcica in the ﬂoor ofthe skull. It’sconnected to

the hypothalamusof the brain by the infundibulum.

Optic chiasm

Pars

tuberalis

Pars

intermedia

Pars

distalis

Anterior pituitary

(adenohypophysis)

Mammillary

body

Infundibulum

Posterior pituitary

(neurohypophysis)

Hypothalamus

Figure 18.2

Subdivisionsof the Pituitary Gland

The pituitarygland is divided into the anterior pituitary, or adenohypophysis,

and the posterior pituitary, or neurohypophysis. The anterior pituitaryis

subdivided further into the parsdistalis, pars intermedia, and pars tuberalis.

The posterior pituitaryconsists of the enlarged distalend of the infundibulum,

which connectsthe posterior pituitary to the hypothalamus.

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anterior pituitary gland (table 18.1).These releasing hormones are

sometimes referred to as releasing or inhibiting factors because

their structure is not certain or because more than one substance

from the hypothalamus is known to act as a releasing or inhibiting

factor.The term hormone has been used in this text, to avoid con-

fusion and because the rapid rate at which new discoveries are

made.Secretions of the anterior pituitary g land are described in a

following section called “Anterior Pituitary Hormones”(p 604).

There is no portal system to carry hypothalamic neurohor-

mones to the posterior pituitary.Neurohormones released from the

posterior pituitary are produced by neurosecretory cells with their

cell bodies located in the hypothalamus.The axons of these cells ex-

tend from the hypothalamus through the infundibulum into the

posterior pituitary and form a nerve tract called the hypothalamo-

hypophysial tract (ﬁgure 18.4). Neurohormones produced in the

hypothalamus pass down these axons in tiny vesicles and are stored

Part3 Integration and ControlSystems600

in secretory vesicles in the enlarged ends ofthe axons. Action poten-

tials originating in the neuron cell bodies in the hypothalamus are

propagated along the axons to the axon terminals in the posterior pi-

tuitary. The action potentials cause the release of neurohormones

from the axon terminals,and they enter the circulatory system. Se-

cretions ofthe posterior pituitary g land are described in a following

section called “Posterior Pituitary Hormones”(p 601).

3. Where is the pituitary gland located? Contrast the

embryonicorigin of the anterior pituitary and the posterior

pituitary.

4. Name the parts of the pituitary gland and the function of

each part.

5. Deﬁne portal system. Describe the hypothalamohypo-

physial portal system. Howdoes the hypothalamus

regulate the secretion of the anteriorpituitary hormones?

Posterior

pituitary

Vein

Releasing

hormones

stimulate

pituitary

hormone

secretions.

Target tissue

or endocrine gland

pituitary

endocrine

cell

Hypothalamo-

hypophysial

portal system

Artery

Optic chiasm

Stimuli integrated within

the nervous system

Stimulatory

Inhibitory

Hypothalamic

neurons

secrete

releasing

hormones.

1.Releasing hormones are secreted

from hypothalamic neurons as a result

of stimuli integrated within the nervous

system.

2.Releasing hormones pass through

the hypothalamohypophysial portal

system to the anterior pituitary.

3.Releasing hormones leave capillaries

and stimulate anterior pituitary cells to

release their hormones.

4.Anterior pituitary hormones are carried

in the blood to their target tissues

(

green arrow

) which, in some cases,

are endocrine glands.

Figure 18.3

Relationship Among the Hypothalamus, Anterior Pituitary, and TargetTissues

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Chapter 18 Endocrine Glands 601

6. List the releasing and inhibiting hormones that are released

from hypothalamicneurons.

7. Describe the hypothalamohypophysial tract, including the

production of neurohormonesin the hypothalamus and

theirsecretion from the posterior pituitary.

PREDICT

Surgicalremoval of the posterior pituitary in experimental animals

resultsin marked symptoms, but these symptoms associated with

hormone shortage are temporary. Explain these results.

Hormones of the

Pituitary Gland

Objective

■ Describe the target tissues, regulation, and responsesto

each of the posteriorand anterior pituitary hormones.

This section describes the hormones secreted from the pitu-

itary gland (table 18.2), their effects on the body,and the mecha-

nisms that regulate their secretion rate. In addition,some major

consequences ofabnormal hormone secretion are stressed.

Posterior PituitaryHormones

The posterior pituitary stores and secretes two polypeptide neuro-

hormones called antidiuretic hormone and oxytocin. A separate

population ofcells secretes each hormone.

AntidiureticHormone

Antidiuretic (ante¯-d-ı¯-u¯-retik) hormone (ADH) is so named

because it prevents (anti-) the output of large amounts of urine

(diuresis).ADH is sometimes called vasopressin (va¯-so¯-presin,

vas-o¯-presin) because it constricts blood vessels and raises blood

pressure when large amounts are released.ADH is synthesized by

neuron cell bodies in the supraoptic nuclei of the hypothalamus

and transported within the axons of the hypothalamohy-

pophysial tract to the posterior pituitary, where it is stored in

axon terminals.ADH is released from these axon terminals into

the blood and carried to its primary target tissue, the kidneys,

where it promotes the retention ofwater and reduces urine vol-

ume (see chapter 26).

The secretion rate for ADH changes in response to alter-

ations in blood osmolality and blood volume.The osmolality of

a solution increases as the concentration of solutes in the solu-

tion increases. Specialized neurons, called osmoreceptors

(osmo¯-re¯ -septerz, osmo¯-re¯-septo¯rz),synapse with the ADH

neurosecretory cells in the hypothalamus.When blood osmolal-

ity increases, the frequency of action potentials in the osmore-

ceptors increases, resulting in a greater frequency of action

potentials in the neurosecretory cells. As a consequence,ADH

secretion increases.Alternatively, an increase in blood osmolal-

ity can directly stimulate the ADH neurosecretory cells.Because

ADH stimulates the kidneys to retain water,it functions to re-

duce blood osmolality and resists any further increase in the os-

molality of body ﬂuids.

As the osmolality of the blood decreases,the action poten-

tial frequency in the osmoreceptors and the neurosecretory cells

decreases.Thus, less ADH is secreted from the posterior pituitary

gland, and the volume of water eliminated in the form of urine

increases.

Urine volume increases within minutes to a few hours in re-

sponse to the consumption ofa large volume of water. In contrast,

urine volume decreases and urine concentration increases within

hours if little water is consumed.ADH plays a major role in these

changes in urine formation.The effect is to maintain the osmolality

Table 18.1

Hormones Structure Target Tissue Response

Growth hormone- Small peptide Anterior pituitary cells that secrete growth Increased growth hormone

releasing hormone hormone secretion

(GHRH)

Growth hormone- Small peptide Anterior pituitary cells that secrete growth Decreased growth

inhibiting hormone hormone hormone secretion

(GHIH), or somatostatin

Thyroid-releasing Small peptide Anterior pituitary cells that secrete Increased thyroid-stimulating

hormone (TRH) thyroid-stimulating hormone hormone secretion

Corticotropin-releasing Peptide Anterior pituitary cells that secrete adrenocorticotropic Increased adrenocorticotropic

hormone (CRH hormone hormone secretion

Gonadotropin-releasing Small peptide Anterior pituitary cells that secrete luteinizing Increased secretion of

hormone (GnRH) hormone and follicle-stimulating luteinizing hormone and

hormone follicle-stimulating hormone

Prolactin-inhibiting Unknown Anterior pituitary cells that secrete prolactin Decreased prolactin

hormone (PIH) (possibly secretion

dopamine)

Prolactin-releasing Unknown Anterior pituitary cells that secrete prolactin Increased prolactin

hormone (PRH) secretion

Hormones of the Hypothalamus

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Part3 Integration and ControlSystems602

Neurohormone

Hypothalamic

neuron

Stimuli integrated within

the nervous system

Hypothalamohypophysial

tract

Optic

chiasm

Posterior

pituitary

Vein

Target tissue

1. Stimuli integrated in the nervous system

stimulate hypothalamic neurons to produce

action potentials.

2. Action potentials are carried by axons

through the hypothalamohypophysial

tract to the posterior pituitary.

3. In the posterior pituitary, action potentials

cause the release of neurohormones

from the axon terminals into the

circulatory system.

4. The neurohormones pass through the

circulatory system and influence the

activity of their target tissues (

green arrow

Stimulatory

Inhibitory

Figure 18.4

Relationship Among the Hypothalamus, Posterior Pituitary, and TargetTissues

and the volume ofthe extracellular ﬂuid within a nor mal range of

values.

Sensory receptors that detect changes in blood pressure send

action potentials through sensory nerve ﬁbers of the vagus nerve

that eventually synapse with the ADH neurosecretory cells.A de-

crease in blood pressure,which normally accompanies a decrease

in blood volume,causes an increased action potential frequency in

the neurosecretory cells and increased ADH secretion, which

stimulates the kidneys to retain water.Because the water in urine is

derived from blood as it passes through the kidneys,ADH slows

any further reduction in blood volume.

An increase in blood pressure decreases the action potential

frequency in neurosecretory cells. This leads to the secretion of

less ADH from the posterior pituitary.As a result, the volume of

urine produced by the kidneys increases (ﬁgure 18.5).The effect

of ADH on the kidney and its role in the regulation of extra-

cellular osmolality and volume are described in greater detail in

chapters 26 and 27.

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Chapter 18 Endocrine Glands 603

DiabetesInsipidus

A lackof ADH secretion is one cause of diabetesinsipidus and leads to

the production ofa large amount of dilute urine, which can approach

20L/day. The loss of many liters of water in the form of urine causesan

increase in the osmolalityof the body ﬂuids, and a decrease in

extracellular ﬂuid volume, butnegative-feedbackmechanisms fail to

stimulate ADH release. The volume ofurine produced each dayincreases

rapidlyas the rate of ADH secretion becomes less than 50% ofnormal.

Diabetesinsipidus can also result from either damage to the kidneys or a

geneticdisorder that makes the kidneysincapable of responding to ADH.

Damage to the nephronscan result from infection or other diseases that

damage the nephronsand make them insensitive to ADH. In genetic

disorderseither the receptor for ADH is abnormal or the intracellular

signalmolecules fail to produce a normal response. The consequences

ofdiabetes insipidus are not obvious until the condition becomes

severe. When the condition issevere, dehydration and death can result

unlessthe intake of water is adequate to accommodate itsloss.

Oxytocin

Oxytocin (ok-se¯-to¯ sin) is synthesized by neuron cell bodies in

the paraventricular nuclei of the hypothalamus and then is trans-

ported through axons to the posterior pituitary,where it is stored

in the axon terminals.

Oxytocin stimulates smooth muscle cells ofthe uterus. This

hormone plays an important role in the expulsion ofthe fetus from

the uterus during delivery by stimulating uterine smooth muscle

contraction.It also causes contraction of uterine smooth muscle in

nonpregnant women, primarily during menses and sexual inter-

course.The uterine contractions play a role in the expulsion of the

uterine epithelium and small amounts ofblood during menses and

can participate in the movement ofsperm cells through the uterus

after sexual intercourse.Oxytocin is also responsible for milk ejec-

tion in lactating females by promoting contraction of smooth

musclelike cells surrounding the alveoli of the mammary glands

(see chapter 29). Little is known about the effect of oxytocin in

males.

Table 18.2

Hormones Structure Target Tissue Response

Posterior Pituitary (Neurohypophysis)

Antidiuretic hormone Small peptide Kidney Increased water reabsorption (less water is lost in the

(ADH) form of urine)

Oxytocin Small peptide Uterus; mammary glands Increased uterine contractions; increased milk expulsion

from mammary glands; unclear function in males

Anterior Pituitary (Adenohypophysis)

Growth hormone (GH), Protein Most tissues Increased growth in tissues; increased amino acid uptake

or somatotropin and protein synthesis; increased breakdown of lipids

and release of fatty acids from cells; increased

glycogen synthesis and increased blood glucose

levels; increased somatomedin production

Thyroid-stimulating Glycoprotein Thyroid gland Increased thyroid hormone secretion

hormone (TSH)

Adrenocorticotropic Peptide Adrenal cortex Increased glucocorticoid hormone secretion

hormone (ACTH)

Lipotropins Peptides Fat tissues Increased fat breakdown

 endorphins Peptides Brain, but not all target tissuesare Analgesia in the brain; inhibition of gonadotropin-

known releasinghormone secretion

Melanocyte-stimulating Peptide Melanocytes in the skin Increased melanin production in melanocytes to make

hormone (MSH) the skin darker in color

Luteinizing hormone Glycoprotein Ovaries in females; testes in males Ovulation and progesterone production in ovaries;

(LH) testosterone synthesis and support for sperm cell

production in testes

Follicle-stimulating Glycoprotein Follicles in ovaries in females; Follicle maturation and estrogen secretion in ovaries;

hormone (FSH) seminiferous tubes in males sperm cell production in testes

Prolactin Protein Ovaries and mammary glands in Milk production in lactating women; increased response

females of follicle to LH and FSH; unclear function in males

Hormones of the Pituitary Gland

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Stretch of the uterus, mechanical stimulation of the cervix,

or stimulation ofthe nipples of the breast when a baby nurses acti-

vate nervous reﬂexes that stimulate oxytocin release.Action poten-

tials are carried by sensory neurons from the uterus and from the

nipples to the spinal cord.Action potentials are then carried up the

spinal cord to the hypothalamus,where they increase action poten-

tials in the oxytocin-secreting neurons.Action potentials in the

oxytocin-secreting neurons pass along the axons in the hypothala-

mohypophysial tract to the posterior pituitary,w here they cause

the axon terminals to release oxytocin.The role of oxytocin in the

reproductive system is described in greater detail in chapter 29.

8. Where is ADH produced, from where is it secreted, and

whatis its target tissue? When ADH levels increase, how

are urine volume, blood osmolality, and blood volume

affected?

9. The secretion rate for ADH changes in response to

alterationsin what two factors? Name the types of sensory

cellsthat respond to alterations in those factors.

10. Where is oxytocin produced and secreted, and what effects

doesit have on its target tissues? What factors stimulate

the secretion of oxytocin?

Part3 Integration and ControlSystems604

Anterior PituitaryHormones

Releasing and inhibiting hormones that pass from the hypothala-

mus through the hypothalamohypophysial portal system to the an-

terior pituitary inﬂuence anterior pituitary secretions. For some

anterior pituitary hormones,the hypothalamus produces both re-

leasing hormones and inhibiting hormones.For others regulation

is primarily by releasing hormones (see table 18.1).

The hormones released from the anterior pituitary are pro-

teins, glycoproteins,or polypeptides. They are transported in the

circulatory system,have a half-life measured in minutes, and bind

to membrane-bound receptor molecules on their target cells.For

the most part, each hormone is secreted by a separate cell type.

Adrenocorticotropic hormone and lipotropin are exceptions be-

cause these hormones are derived from the same precursor protein.

Anterior pituitary hormones are called tropic (tropik,

tro¯ pik) hormones. They are released from the anterior pituitary

gland and regulate target tissues including the secretion of hor-

mones from other endocrine glands.The tropic hormones include

growth hormone, adrenocorticotropic hormone and related sub-

stances, luteinizing hormone, follicle-stimulating hormone,pro-

lactin,and thyroid-stimulating hormone.

An increase in blood osmolality or a

decrease in blood volume affects

neurons in the hypothalamus,

resulting in an increase in ADH

release from the posterior pituitary.

A decrease in blood osmolality or an

increase in blood volume affects

neurons in the hypothalamus,

resulting in a decrease in ADH

release from the posterior pituitary.

Reduced ADH decreases water

reabsorption in the kidney, resulting in

reduction of the volume of water in the

blood, increased urine volume, and

increased blood osmolality. There is

also a decrease in blood volume.

ADH increases water reabsorption in

the kidney, resulting in retention of a

greater volume of water in the blood,

a reduced urine volume, and

decreased blood osmolality. There is

also an increase in blood volume.

Hypothalamic

neuron

Posterior pituitary

ADH

Decreased

ADH secretion

Increased

ADH secretion

Kidney

Stimulatory

Inhibitory

Figure 18.5

Controlof Antidiuretic Hormone (ADH) Secretion

The relationship among blood osmolality, blood volume, ADH secretion, and kidneyfunction. Smallchanges in blood osmolality are important in regulating ADH

secretion. Larger changesin blood volume are required to inﬂuence ADH secretion.

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Chapter 18 Endocrine Glands 605

Growth Hormone

Growth hormone (GH), sometimes called somatotropin

(so¯ ma˘-to¯-tro¯pin),stimulates growth in most tissues, plays a ma-

jor role in regulating growth, and therefore,plays an important

role in determining how tall a person becomes.It is also a regulator

of metabolism.GH increases the number of amino acids entering

cells and favors their incorporation into proteins.It increases lipol-

ysis,or the breakdown of lipids and the release of fatt y acids from

fat cells. Fatty acids then can be used as energy sources to drive

chemical reactions,including anabolic reactions, by other cells.GH

increases glycogen synthesis and storage in tissues, and the in-

creased use offats as an energy source spares glucose. GH plays an

important role in regulating blood nutrient levels after a meal and

during periods of fasting.

GH binds directly to membrane-bound receptors on target

cells (see chapter 17),such as fat cells, to produce responses. These

responses are called the direct effects of GH and include the in-

creased breakdown oflipids and decreased use of glucose as an en-

ergy source.

GH also has indirect effects on some tissues.It increases the

production of a number of polypeptides, primarily by the liver

but also by skeletal muscle and other tissues.These polypeptides,

called somatomedins (so¯ma˘-to¯-me¯ dinz), circulate in the

blood and bind to receptors on target tissues. The best under-

stood effects of the somatomedins are the stimulation of growth

in cartilage and bone and the increased synthesis of protein in

skeletal muscles. The best known somatomedins are two

polypeptide hormones produced by the liver called insulinlike

growth factor Iand II because of the similarity of their str ucture

to insulin and because the receptor molecules function through a

mechanism similar to the receptors for insulin.Growth hormone

and growth factors, like somatomedins, bind to membrane-

bound receptors that phosphorylate intracellular proteins (see

chapter 17).

Two neurohormones released from the hypothalamus regu-

late the secretion of GH (figure 18.6). One factor, growth

hormone-releasing hormone (GHRH),stimulates the secretion of

GH, and the other, growth hormone-inhibiting hormone

(GHIH),or somatostatin (so¯ma˘-to¯-statin), inhibits the secre-

tion of GH.Stimuli that inﬂuence GH secretion act on the hypo-

thalamus to increase or decrease the secretion ofthe releasing and

inhibiting hormones. Low blood glucose levels and stress stimu-

late secretion of GH,and high blood g lucose levels inhibit secre-

tion of GH. Rising blood levels of certain amino acids also

increases GH secretion.

In most people,a rhythm of GH secretion occurs. Daily peak

levels of GH are correlated with deep sleep.A chronically elevated

blood GH level during periods of rapid growth does not occur,al-

though children tend to have somewhat higher blood levels ofGH

than adults.In addition to GH, factors like genetics, nutrition, and

sex hormones inﬂuence growth.

Several pathologic conditions are associated with abnormal

GH secretion. In general, the causes for hypersecretion or

hyposecretion of GH are the result of tumors in the hypothala-

mus or pituitary,the synthesis of structurally abnormal GH, the

inability of the liver to produce somatomedins, or the lack of

functional receptors in target tissues.The consequences of hyper-

secretion and hyposecretion ofgrowth hormone are described in

the Clinical Focus on “Growth Hormone and Growth Disorders”

(page 606);also see chapter 6.

PREDICT

Mr. Hoopshas a son who wants to be a basketballplayer almost as

much asMr. Hoops wantshim to be one. Mr. Hoops knows a little bit

aboutgrowth hormone and asks his son’s doctor if he would prescribe

some for hisson, so he can grow tall. What do you thinkthe doctor

tellsMr. Hoops?

Increased growth

hormone-releasing

hormone (GHRH)

Decreased growth

hormone-inhibiting

hormone (GHIH)

Target tissue

• Increases protein synthesis

• Increases tissue growth

• Increases fat breakdown

• Spares glucose usage

pituitary

Stress

Low blood glucose

Stimulatory

Inhibitory

Figure 18.6

Controlof Growth Hormone (GH) Secretion

Secretion ofGH is controlled by two neurohormones released from the

hypothalamus: growth hormone-releasing hormone (GHRH), which stimulates

GH secretion, and growth hormone-inhibiting hormone (GHIH), which inhibits

GH secretion. Stressincreases GHRH secretion and inhibits GHIH secretion.

High levelsof GH have a negative-feedback effect on the production ofGHRH

bythe hypothalamus.

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AdrenocorticotropicHormone and

Related Substances

Adrenocorticotropic (a˘-dre¯ no¯-ko¯rti-ko¯-tro¯ pik) hor mone

(ACTH)is one of several anterior pituitary hormones derived from

a precursor molecule called proopiomelanocortin (pro¯-o¯pe¯-o¯-

mela˘-no¯-ko¯rtin). This large molecule gives rise to ACTH,

lipotropins, endorphin, and melanocyte-stimulating hormone.

ACTH binds to membrane-bound receptors and activates a

G protein mechanism that increases cAMP,which produces a re-

sponse.ACTH increases the secretion of hormones, primarily cor-

tisol,from the adrenal cortex. ACTH and melanocyte-stimulating

hormone also bind to melanocytes in the skin and increase skin

pigmentation (see chapter 5).In pathologic conditions like Addi-

son’s disease,blood levels of ACTH and related hormones are

chronically elevated,and the skin becomes markedly darker.Regu-

lation ofACTH secretion and the effect of hypersecretion and hy-

posecretion of ACTH are described in the section on “Adrenal

Glands’’on page 615.

Thelipot ropins (li-po¯-tro¯pinz) secreted from the anterior

pituitary bind to membrane-bound receptor molecules on adipose

Thyroid-Stimulating Hormone

Thyroid-stimulating hormone (TSH), also called thyrotropin

(thı¯-rotro¯-pin, thı¯-ro¯-tro¯pin), stimulates the synthesis and se-

cretion ofthyroid hormones from the thyroid gland. TSH is a gly-

coprotein consisting of  and  subunits, which bind to

membrane-bound receptors ofthe thyroid gland. The receptors re-

spond through a G protein mechanism that increases the intracel-

lular chemical signal, cAMP.In higher concentrations, TSH also

increases the activity of phospholipase. Phospholipase activates

mechanisms that open Ca

channels and increases the Ca

con-

centration in cells ofthe thyroid gland (see chapter 17).

TSH secretion is controlled by TRH from the hypothalamus

and thyroid hormones from the thyroid gland. TRH binds to

membrane-bound receptors in cells ofthe anterior pituitary gland

and activates G proteins,which results in increased TSH secretion.

In contrast,thyroid hormones inhibit both TRH and TSH secre-

tion.TSH is secreted in a pulsatile fashion and its blood levels are

highest at night,but it’s secreted at a rate so that blood levels of thy-

roid hormones are maintained within a narrow range of values

(see “Thyroid Hormones’’p 608).

Clinical Focus Growth Hormone and Growth Disorders

Chronichyposecretion of GH in infants and

children leads to dwarﬁsm (dwo¯rfizm), or

short stature due to delayed bone growth.

The bones usually have a normal shape,

however. In contrastto dwarﬁsm caused by

hyposecretion of thyroid hormones, these

dwarfs exhibit normal intelligence. Other

symptomsresulting from the lack of GH in-

clude mild obesity and retarded develop-

ment of adult reproductive functions. Two

types of dwarﬁsm result from a lackof GH

secretion: (1) In approximatelytwo-thirds of

the cases, GH and other anterior pituitary

hormones are secreted in reduced

amounts. The decrease in other anterior pi-

tuitary hormones can result in additional

disorders, such asreduced secretion of thy-

roid hormones and inability to reproduce;

(2) in the remaining approximately one-

third of cases, a reduced amountof GH is

observed, and the secretion of other ante-

rior pituitaryhormones is closer to normal.

Normal reproduction is possible for these

individuals. No obviouspathology is asso-

ciated with hyposecretion of GH in adults,

although some evidence suggeststhat lack

of GH can lead to reduced bone mineral

contentin adults.

The gene responsible for determining

the structure of GH has been transferred

successfullyfrom human cells to bacterial

cells, which produce GH thatis identical to

human GH. The GH produced in thisfashion

isavailable to treat patients who suffer from

a lackof GH secretion.

Chronichypersecretion of GH leads to

giantism (jı¯an-tizm) or acromegaly(ak-ro¯-

mega˘-le¯), depending on whether the hy-

persecretion occurs before or after

complete ossiﬁcation of the epiphysial

plates in the skeletal system. Chronichy-

persecretion of GH before the epiphysial

plates have ossiﬁed causes exaggerated

and prolonged growth in long bones, result-

ing in giantism. Some individuals thusaf-

fected have grown to be 8 feettall or more.

In adults, chronicallyelevated GH lev-

els result in acromegaly. No increase in

height occurs because ofthe ossiﬁed epi-

physialplates. The condition does result in

an increased diameter of ﬁngers, toes,

hands, and feet; the deposition of heavy

bony ridges above the eyes; and a promi-

nentjaw. The inﬂuence ofGH on soft tissues

results in a bulbousor broad nose, an en-

larged tongue, thickened skin, and sparse

subcutaneous adipose tissue. Nerves fre-

quently are compressed as a resultof the

proliferation ofconnective tissue. Because

GH spares glucose usage, chronic hyper-

glycemia results, frequentlyleading to dia-

betes mellitus and the development of

severe atherosclerosis. Treatment for

chronichypersecretion of GH often involves

surgical removal or irradiation of a GH-

producing tumor.

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tissue cells.They cause fat breakdown and the release of fatty acids

into the circulatory system.

The ␤ endorphins (endo¯r-ﬁnz) have the same effects as

opiate drugs like morphine,and they can play a role in analgesia in

response to stress and exercise.Other functions have been pro-

posed for the endorphins, including regulation of body temper-

ature, food intake, and water balance. Both ACTH and

-endorphin secretions increase in response to stress and exercise.

Melanocyte-stimulating hormone (MSH) binds to

membrane-bound receptors on skin melanocytes and stimulates

increased melanin deposition in the skin.The regulation of MSH

secretion and its function in humans is not well understood,

although it’s an important regulator ofskin pigmentation in some

other vertebrates.

Luteinizing Hormone, Follicle-Stimulating

Hormone, and Prolactin

Gonadotropins (go¯nad-o¯-tro¯pinz) are hormones capable of

promoting growth and function ofthe gonads, which include the

ovaries and testes.The two major gonadotropins secreted from the

anterior pituitary are luteinizing (loote¯-ı˘-nı¯z-ing)hormone

(LH)and follicle-stimulating hormone (FSH). LH, FSH, and an-

other anterior pituitary hormone called prolactin (pro¯-laktin)

play important roles in regulating reproduction.

LH and FSH secreted into the blood bind to membrane-

bound receptors, increase the intracellular synthesis of cAMP

through G protein mechanisms,and stimulate the production of

gametes (game¯ts)—sperm cells in the testes and oocytes in

ovaries.LH and FSH also control the production of reproductive

hormones—estrogens and progesterone in the ovaries and testos-

terone in the testes.

LH and FSH are released from anterior pituitary cells un-

der the influence of the hypothalamic-releasing hormone,

gonadotropin-releasing hormone (GnRH). GnRH is also called

luteinizing hormone-releasing hormone (LHRH).

Prolactin plays an important role in milk production in the

mammary glands of lactating females. It binds to a membrane-

bound receptor that phosphorylates intracellular proteins. The

phosphorylated proteins produce the response in the cell. Pro-

lactin can also increase the number of receptor molecules for

FSH and LH in the ovaries (up regulation),and it therefore has a

permissive effect for FSH and LH on the ovary.Prolactin also can

enhance progesterone secretion ofthe ovar y after ovulation.No

role for this hormone has been clearly established in males.Sev-

eral hypothalamic neurohormones can be involved in the com-

plex regulation of prolactin secretion. One neurohormone is

prolactin-releasing hormone (PRH), and another is prolactin-

inhibiting hormone (PIH).The regulation of gonadotropin and

prolactin secretion and their speciﬁc effects are explained more

fully in chapter 28.

11. Structurally, what kind of hormones are released from the

posteriorpituitary and the anterior pituitary? Do these

hormonesbind to plasma proteins, how long is their half-

life, and howdo they activate their target tissues?

12. For each of the following hormones secreted by the anterior

pituitary

—

GH, TSH, ACTH, LH, FSH, and prolactin

—

name

itstarget tissue and the effect of the hormone on its target

tissue.

13. What effects do stress, amino acid levels in the blood, and

glucose levelsin the blood have on GH secretion?

14. What stimulates somatomedin production, where is it

produced, and whatare its effects?

15. How are ACTH, MSH, lipotropins, and

␤

endorphinsrelated?

Whatare the functions of these hormones?

16. Deﬁne gonadotropins, and name two gonadotropins

produced bythe anterior pituitary.

Thyroid Gland

Objectives

■ Describe the histology and location of the thyroid gland

and describe the synthesisand transport of thyroid

hormones.

■ Explain the response of target tissues to thyroid hormones,

and outline the regulation of thyroid hormone secretion.

■ Explain the regulation of calcitonin secretion, and describe

itsfunction.

Thethyroid gland is composed of two lobes connected by a

narrow band ofthyroid tissue called the isthmus. The lobes are lat-

eral to the upper portion of the trachea just inferior to the larynx,

and the isthmus extends across the anterior aspect of the trachea

(ﬁgure 18.7a). The thyroid gland is one of the largest endocrine

glands, with a weight of approximately 20 g. It is highly vascular

and appears more red than its surrounding tissues.

Histology

The thyroid gland contains numerous follicles, which are small

spheres whose walls are composed of a single layer of cuboidal ep-

ithelial cells (ﬁgure 18.7band c).The center, or lumen, of each thyroid

follicle is ﬁlled with a protein called thyroglobulin (thı¯-ro¯-globu¯-

lin) to which thyroid hormones are bound.Because of thyroglobulin

the follicles store large amounts ofthe thyroid hormones.

Between the follicles,a delicate network of loose connective

tissue contains numerous capillaries. Scattered parafollicular

(par-a˘ -fo-liku¯ -la˘r) cells are found between the follicles and

among the cells that make up the walls of the follicle.Calcitonin

(kal-si-to¯ nin) is secreted from the parafollicular cells and plays a

role in reducing the concentration of calcium in the body ﬂuids

when calcium levels become elevated.

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Parafollicular cell

Parafollicular

cells

Thyroid follicle

(containing thyroglobulin)

Follicular

cells

LM 130x

Superior

thyroid artery

Larynx

Thyroid gland

Isthmus

Common

carotid artery

Inferior

thyroid artery

Trachea

Figure 18.7

Anatomyand Histology of the Thyroid Gland

(a) Frontalview of the thyroid gland. (b) Histology of the thyroid gland. The

gland ismade up of many spheric thyroid follicles containing thyroglobulin.

Parafollicular cellsare in the tissue between the thyroid follicles. (c) Low-

power photomicrograph ofthyroid follicles.

(a)

(b)

(c)

Thyroid Hormones

The thyroid hormones include both triiodothyronine (trı¯-ı¯o¯-

do¯ -thı¯ro¯-ne¯n;T

) andtetraiodothyronine (tetra˘-ı¯o¯-do¯-thı¯ro¯-

ne¯n; T

). T

is also called thyroxine (thı¯-rokse¯n, thı¯-roksin).

These substances constitute the major secretory products of the

thyroid gland,consisting of 10% T

and 90% T

(table 18.3).

Thyroid Hormone Synthesis

Thyroid-stimulating hormone (TSH) from the anterior pitu-

itary must be present to maintain thyroid hormone synthesis

and secretion. TSH causes an increase in synthesis of thyroid

hormones, which are then stored inside of the thyroid follicles

attached to thyroglobulin.Also, some of the thyroid hormones

are released from thyroglobulin and enter the circulatory sys-

tem.An adequate amount of iodine in the diet also is required

for thyroid hormone synthesis.The following events in the thy-

roid follicles result in thyroid hormone synthesis and secretion

(ﬁgure 18.8):

1. Iodide ions (I



) are taken up by thyroid follicle cells by

active transport.The active transport of the I



is against a

concentration gradient ofapproximately 30-fold in healthy

individuals.

2. Thyroglobulins,which contain numerous tyrosine amino

acid molecules,are synthesized within the cells of the follicle.

3. Nearly simultaneously,the I



are oxidized to form iodine (I)

and either one or two iodine atoms are bound to each ofthe

tyrosine molecules ofthyroglobulin. This occurs close to the

time the thyroglobulin molecules are secreted by the process

ofexocytosis into the lumen of the follicle. As a result, the

secreted thyroglobulin contains many iodinated tyrosines.

4. In the lumen ofthe follicle, two diiodotyrosine molecules of

thyroglobulin combine to form tetraiodothyronine (T

),or

one monoiodotyrosine and one diiodotyrosine molecule

combine to form triiodothyronine (T

).Large amounts of

and T

are stored within the thyroid follicles as part of

thyroglobulin.A reserve sufﬁcient to supply thyroid

hormones for approximately 2 weeks is stored in this form.

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Wall of thyroid follicle Lumen of thyroid follicle

Iodide is actively

transported into

thyroid follicle

cells.

Thyroid

gland

Thyroid

follicle

cell

ATP

ADP

Tyrosine amino acids

are iodinated within the

thyroglobulin molecule.

Thyroglobulin

is synthesized

in the thyroid

follicle cell.

Lysosomes

Amino acids

Amino acid pool

(including

tyrosine)

Thyroglobulin breaks down to individual amino acids and

and T

. T

and T

diffuse out of the thyroid follicle and

enter the circulatory system.

Endocytosis of

thyroglobulin into

the thyroid follicle cells.

and T

are part of

thyroglobulin in the

lumen of the follicle.

Two iodinated tyrosine

amino acids of

thyroglobulin join to form

tetraiodothyronine (T

)

or triiodothyronine (T

ProcessFigure 18.8

Biosynthesisof Thyroid Hormones

The numbered stepsdescribe the synthesis and the secretion of thyroid hormones from the thyroid gland. See textfor details of each numbered step.

Table 18.3

Hormones Structure Target Tissue Response

Thyroid Gland

Thyroid Follicles

Thyroid hormones Amino acid Most cells of the body Increased metabolic rate; essential for normal process of growth

(triiodothyronine derivative and maturation

and tetraiodothyronine)

Parafollicular Cells

Calcitonin Polypeptide Bone Decreased rate of breakdown of bone by osteoclasts; prevention

of a large increase in blood calcium levels

Parathyroid

Parathyroid hormone Peptide Bone; kidney; Increased rate of breakdown of bone by osteoclasts; increased

small intestine reabsorption of calcium in kidneys; increased absorption of

calcium from the small intestine; increased vitamin D synthesis;

increased blood calcium levels

Hormones of the Thyroid and Parathyroid Glands

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5. Thyroglobulin is taken into the thyroid follicle cells by

endocytosis where lysosomes fuse with the endocytotic

vesicles.

6. Proteolytic enzymes break down thyroglobulin to release T

and T

,which then diffuse from the follicular cells into the

interstitial spaces and ﬁnally into the capillaries ofthe

thyroid gland.The remaining amino acids of thyroglobulin

are used again to synthesize more thyroglobulin.

Transportin the Blood

Thyroid hormones are transported in combination with plasma

proteins in the circulatory system.Approximately 70%–75% of the

circulating T

and T

are bound to thyroxine-binding globulin

(TBG), which is synthesized by the liver and 20% to 30% are

bound to other plasma proteins, including albumen.T

and T

bound to these plasma proteins,form a large reservoir of circulat-

ing thyroid hormones, and the half-life of these hormones is in-

creased greatly because of this binding. After thyroid gland

removal in experimental animals,it takes approximately 1 week for

and T

levels in the blood to decrease by 50%.As free T

and T

levels decrease in the interstitial spaces,additional T

and T

disso-

ciate from the plasma proteins to maintain the levels in the tissue

spaces. When sudden secretion of T

and T

occurs, the excess

binds to the plasma proteins.As a consequence, the concentration

ofthyroid hormones in the tissue spaces ﬂuctuates very little.

Approximately 33%–40% ofthe T

is converted to T

in the

body tissues. This conversion can be important in the action of

thyroid hormones on their target tissues because T

is the major

hormone that interacts with target cells.In addition, T

is several

times more potent than T

Much of the circulating T

is eliminated from the body by

being converted to tetraiodothyroacetic acid and then excreted in

the urine or bile.In addition, a large amount is converted to an in-

active form ofT

and rapidly metabolized and excreted.

Mechanism of Action of Thyroid Hormones

Thyroid hormones interact with their target tissues in a fashion sim-

ilar to that of the steroid hormones. They readily diffuse through

plasma membranes into the cytoplasm of cells. Within cells,they

bind to receptor molecules in the nuclei.Thyroid hormones com-

bined with their receptor molecules interact with DNA in the nu-

cleus to inﬂuence regulatory genes and initiate new protein synthesis.

The newly synthesized proteins within the target cells mediate the re-

sponse ofthe cells to thyroid hormones. It takes up to a week after the

administration of thyroid hormones for a maximal response to de-

velop,and new protein synthesis occupies much of that time.

Effectsof Thyroid Hormones

Thyroid hormones affect nearly every tissue in the body,but not all

tissues respond identically.Metabolism is primarily affected in

some tissues,and growth and maturation are inﬂuenced in others.

The normal rate ofmetabolism for an individual depends on

an adequate supply ofthyroid hormone, which increases the rate at

which glucose, fat, and protein are metabolized.Blood levels of

cholesterol decline. Thyroid hormones increase the activity of

–K

exchange pump,which contributes to an increase in body

temperature.Thyroid hormones can alter the number and activity

Part3 Integration and ControlSystems610

of mitochondria, resulting in greater ATP and heat production.

The metabolic rate can increase from 60%–100% when blood thy-

roid hormones are elevated.Low levels of thyroid hormones lead

to the opposite effect. Normal body temperature depends on an

adequate amount ofthyroid hormone.

Normal growth and maturation of organs also depend on

thyroid hormones.For example, bone, hair, teeth, connective tis-

sue, and nervous tissue require thyroid hormone for normal

growth and development.Both normal growth and normal matu-

ration of the brain require thyroid hormones. Also,thyroid hor-

mones play a permissive role for GH,and GH does not have its

normal effect on target tissues ifthyroid hormones are not present.

The speciﬁc effects of hyposecretion and hypersecretion of

thyroid hormones are outlined in table 18.4. Hypersecretion of

thyroid hormones increases the rate of metabolism. High body

temperature,weight loss, increased appetite, rapid heart rate, and

an enlarged thyroid gland are major symptoms.

Hyposecretion of thyroid hormone decreases the rate of me-

tabolism.Low body temperature, weight gain, reduced appetite, re-

duced heart rate,reduced blood pressure, weak skeletal muscles, and

apathy are major symptoms.If hyposecretion of thyroid hormones

occurs during development there is a decreased rate ofmetabolism,

abnormal nervous system development, abnormal growth,and ab-

normal maturation oftissues. The consequence is a mentally retarded

person ofshort stature and distinctive form called a cretin (kre¯tin).

Regulation of Thyroid Hormone Secretion

Thyroid-releasing hormone (TRH) from the hypothalamus and

TSH from the anterior pituitary function together to increase T

and T

secretion from the thyroid gland.Exposure to cold and stress

cause increased TRH secretion and prolonged fasting decreases

TRH secretion.TRH stimulates the secretion of TSH from the ante-

rior pituitary.When TRH release increases, TSH secretion from the

anterior pituitary gland also increases. When TRH release de-

creases,TSH secretion decreases. Small ﬂuctuations in blood levels

ofTSH occur on a daily basis, with a small nocturnal increase. TSH

stimulates T

and T

secretion from the thyroid gland.TSH also in-

creases the synthesis of T

and T

as well as causing hypertrophy

(increased cell size) and hyperplasia (increased cell number) ofthe

thyroid gland.Decreased blood levels of TSH lead to decreased T

and T

secretion and thyroid gland atrophy.Figure 18.9 illustrates

the regulation ofT

and T

secretion.The thyroid hormones have a

negative-feedback effect on the hypothalamus and anterior pitu-

itary gland. As T

and T

levels increase in the circulatory system,

they inhibit TRH and TSH secretion.Also, if the thyroid gland is re-

moved or ifT

and T

secretion declines,TSH levels in the blood in-

crease dramatically.

Abnormal thyroid conditions are outlined in table 18.5.Hy-

pothyroidism,or reduced secretion of thyroid hormones, can re-

sult from iodine deﬁciency,taking certain drugs, and exposure to

other chemicals that inhibit thyroid hormone synthesis.It can also

be due to inadequate secretion of TSH, an autoimmune disease

that depresses thyroid hormone function, or surgical removal of

the thyroid gland.Hypersecretion of thyroid hormones can result

from the synthesis ofan immune globulin that can bind to TSH re-

ceptors and acts like TSH,and from TSH-secreting tumors of the

pituitary gland.

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Stress, hypothermia

TRH

Hypothalamus

pituitary

Thyroid gland

and T

TSH

Target tissue

•

Increases metabolism

•

Increases body temperature

•

Increases normal growth and

development

1. Thyroid-releasing hormone (TRH) is released from neurons

within the hypothalamus into the blood. It passes through

the hypothalamohypophysial portal system to the anterior

pituitary.

2. TRH causes cells of the anterior pituitary to secrete thyroid-

stimulating hormone (TSH).

3. TSH passes through the general circulation to the thyroid

gland, where it causes both increased synthesis and

secretion of thyroid hormones (T

and T

4. T

and T

have an inhibitory effect on the secretion of TRH

from the hypothalamus and TSH from the anterior pituitary.

Hypothalamohypophysial

portal system

Stimulatory

Inhibitory

ProcessFigure 18.9

Regulation ofThyroid Hormone (T

and T

) Secretion

Table 18.4

Hypothyroidism

Effects of Hyposecretion and Hypersecretion of Thyroid Hormones

Decreased metabolic rate, low body temperature, cold intolerance

Weight gain, reduced appetite

Reduced activity of sweat and sebaceous glands, dry and cold skin

Reduced heart rate, reduced blood pressure, dilated and enlarged

heart

Weak, flabby skeletal muscles, sluggish movements

Constipation

Myxedema (swelling of the face and body) as a result of

mucoprotein deposits

Apathetic, somnolent

Coarse hair, rough and dry skin

Decreased iodide uptake

Possible goiter (enlargement of the thyroid gland)

Hyperthyroidism

Increased metabolic rate, high body temperature, heat intolerance

Weight loss, increased appetite

Copious sweating, warm and flushed skin

Rapid heart rate, elevated blood pressure, abnormal electrocardiogram

Weak skeletal muscles that exhibit tremors, quick movements with exaggerated

reflexes

Bouts of diarrhea

Exophthalmos (protruding of the eyes) as a result of mucoprotein and other deposits

behind the eye

Hyperactivity, insomnia, restlessness, irritability, short attention span

Soft, smooth hair and skin

Increased iodide uptake

Almost always develops goiter

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Goiter and Exophthalmos

An abnormalenlargement of the thyroid gland is called a goiter.Goiters

can resultfrom conditions that cause hypothyroidism as wellas

conditionsthat cause hyperthyroidism. An iodine deﬁciency goiter

resultswhen dietary iodine intake is very low and there is too little

iodine to synthesize T

and T

(see table 18.5). Asa result, blood levels

ofT

and T

decrease and the person mayexhibit symptoms of hypothy-

roidism. The reduced negative feedbackofT

and T

on the anterior

pituitaryand hypothalamus result in elevated TSH secretion. TSH causes

hypertrophyand hyperplasia of the thyroid gland and increased

thyroglobulin synthesiseven though there is not enough iodine to

synthesize T

and T

. Consequently, the thyroid gland enlarges. Toxic

goitersecretes excess T

and T

, and itcan result from elevated TSH

secretion or elevated TSH-like immune globulin molecules(see Graves’

disease in table 18.5). Toxicgoiter resultsin elevated T

and T

secretion

and symptomsof hyperthyroidism. Exophthalmos often accompanies

hyperthyroidism and iscaused by the deposition of excessconnective

tissue proteinsbehind the eyes. The excesstissue makes the eyes move

anteriorly, and consequentlythey appear to be larger than normal.

Gravesdisease is the most common cause of hyperthyroidism.

Elevated T

and T

resulting from thiscondition suppresses TSH and TRH,

butthe T

and T

levelsremain elevated. Exophthalmos is common.

Treatmentoften involves removal of the thyroid gland followed bythe

oraladministration of the appropriate amount of T

and T

. Unfortunately

removalof the thyroid gland normally does not reverse exophthalmos.

PREDICT

Predictthe effect of surgical removal of the thyroid gland on blood

levelsof TRH, TSH, T

and T

. Predictthe effect of oral administration

ofT

and T

on TRH and TSH.

Part3 Integration and ControlSystems612

Calcitonin

The parafollicular cells of the thyroid gland, which secrete calci-

tonin, are dispersed between the thyroid follicles throughout the

thyroid gland.The major stimulus for increased calcitonin secre-

tion is an increase in calcium levels in the body ﬂuids.

The primary target tissue for calcitonin is bone (see chapter

6).Calcitonin binds to membrane-bound receptors, decreases os-

teoclast activity,and lengthens the life span of osteoblasts. The re-

sult is a decrease in blood calcium and phosphate levels caused by

increased bone deposition.

The importance of calcitonin in the regulation of blood cal-

cium levels is unclear.Its rate of secretion increases in response to

elevated blood calcium levels,and it may function to prevent large

increases in blood calcium levels following a meal.Blood levels of

calcitonin decrease with age to a greater extent in females than

males.Osteoporosis increases with age and occurs to a greater de-

gree in females than males.Complete thyroidectomy does not result

in high blood calcium levels,however. It’s possible that the regula-

tion ofblood calcium levels by other hormones, such as parathyroid

hormone,and vitamin D compensates for the loss of calcitonin in

individuals who have undergone a thyroidectomy.No pathologic

condition is associated directly with a lack ofcalcitonin secretion.

17. Where is the thyroid gland located? Describe the follicles

and the parafollicularcells within the thyroid. What

hormonesdo they produce?

18. Starting with the uptake of iodide by the follicles, describe

the production and secretion of thyroid hormones.

19. How are the thyroid hormones transported in the blood?

Whateffect does this transportation have on their half-life?

Table 18.5

Cause Description

Abnormal Thyroid Conditions

Hypothyroidism

Iodine deficiency Causes inadequate thyroid hormone synthesis, which results in elevated thyroid-stimulating hormone

(TSH) secretion; thyroid gland enlarges (goiter) asa result of TSH stimulation; thyroid hormones

frequently remain in the low to normal range

Goiterogenic substances Found in certain drugs and in small amounts in certain plants such as cabbage; inhibit thyroid hormone synthesis

Cretinism Caused by maternal iodine deficiency or congenital errors in thyroid hormone synthesis; results in mental

retardation and a short, grotesque appearance

Lack of thyroid gland Removed surgically or destroyed as a treatment for Graves’ disease (hyperthyroidism)

Pituitary insufficiency Results from lack of TSH secretion; often associated with inadequate secretion of other adenohypophyseal

hormones

Hashimoto’s disease Autoimmune disease in which thyroid function is normal or depressed

Hyperthyroidism (Toxic goiter)

Graves’ disease Characterized by goiter and exophthalmos; apparently an autoimmune disease; most patients have long-acting

thyroid stimulator, a TSH-like immune globulin, in their plasma

Tumors—benign adenoma or cancer Result in either normal secretion or hypersecretion of thyroid hormones(rarely hyposecretion)

Thyroiditis—a viral infection Produces painful swelling of the thyroid gland with normal or slightly increased thyroid hormone production

Elevated TSH levels Result from a pituitary tumor

Thyroid storm Sudden release of large amounts of thyroid hormones; caused by surgery, stress, infections, and unknown

reasons

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20. What are the target tissues of thyroid hormone? By what

mechanism do thyroid hormonesalter the activities of their

targettissues? What effects are produced?

21. Starting in the hypothalamus, explain how chronic

exposure to cold, food deprivation, orstress can affect

thyroid hormone production.

22. Diagram two negative-feedback mechanisms involving

hormonesthat function to regulate production of thyroid

hormones.

23. What effect does calcitonin have on osteoclasts,

osteoblasts, and blood calcium levels? Whatstimulus can

cause an increase in calcitonin secretion?

Parathyroid Glands

Objectives

■ Explain the activity of parathyroid hormone, and describe

the meansby which its secretion is regulated.

■ Explain the relationship between parathyroid hormone and

vitamin D.

Theparathyroid (par-a˘ -thı¯royd)glandsare usually embed-

ded in the posterior part of each lobe of the thyroid gland. Usually

four parathyroid glands are present, with their cells organized in

densely packed masses or cords rather than in follicles (ﬁgure 18.10).

The parathyroid glands secrete parathyroid hormone

(PTH),a polypeptide hormone that is important in the regulation

ofcalcium levels in body ﬂuids (see table 18.3). Bone, the kidneys,

and the intestine are its major target tissues.Parathyroid hormone

binds to membrane-bound receptors and activates a G protein

mechanism that increases intracellular cAMP levels in target tis-

sues. Without functional parathyroid glands,the ability to ade-

quately regulate blood calcium levels is lost.

PTH stimulates osteoclast activity in bone and can cause the

number ofosteoclasts to increase. The increased osteoclast activity

results in bone resorption and the release of calcium and phos-

phate,causing an increase in blood calcium levels. PTH receptors

are not present on osteoclasts but are present on osteoblasts and on

red bone marrow stromal (stem) cells.PTH binds to receptors on

osteoblasts which then promote an increase in osteoclast activity

(see chapter 6).

PTH induces calcium reabsorption within the kidneys so

that less calcium leaves the body in urine.It also increases the en-

zymatic formation of active vitamin D in the kidneys. Calcium is

actively absorbed by the epithelial cells ofthe small intestine, and

the synthesis of transport proteins in the intestinal cells requires

active vitamin D.PTH increases the rate of active vitamin D syn-

thesis,which in turn increases the rate of calcium and phosphate

absorption in the intestine, thereby elevating blood levels of

calcium.

Although PTH increases the release ofphosphate ions (PO

3

)

from bone and increases PO

3

absorption in the gut, it increases

3

excretion in the kidney.The overall effect ofPTH is to decrease

blood phosphate levels.A simultaneous increase in both Ca

2

and

3

results in the precipitation ofcalcium phosphate in soft tissues

ofthe body, where they cause irritation and inﬂammation.

Thyroid follicles

Parathyroid

gland

LM 100x

Pharynx

Posterior aspect

of thyroid gland

Esophagus

Trachea

Parathyroid

glands

Inferior thyroid

artery

Figure 18.10

Anatomyand Histology of the Parathyroid

Glands

(a) The parathyroid glandsare embedded in the posterior part of the

thyroid gland. (b) The parathyroid glandsare composed of densely packed

cordsof cells .

The regulation of PTH secretion is outlined in ﬁgure 18.11.

The primary stimulus for the secretion of PTH is a decrease in

blood Ca

2

levels,whereas elevated blood Ca

2

levels inhibit PTH

secretion. This regulation keeps blood Ca

2

levels ﬂuctuating

within a normal range of values. Both hypersecretion and hypose-

cretion ofPTH cause serious symptoms (table 18.6). The regulation

ofblood Ca

2

levels is discussed more thoroughly in chapter27.

(a)

(b)

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PREDICT

Predictthe effect of an inadequate dietary intake of calcium on PTH

secretion and on targettissues for PTH.

Inactive parathyroid glands result in hypocalcemia.Reduced

extracellular calcium levels cause voltage-gated Na



channels in

plasma membranes to open, which increases the permeability of

plasma membranes to Na



. As a consequence,Na



diffuse into

cells and cause depolarization (see chapter 11). Symptoms of

hypocalcemia are nervousness, muscle spasms, cardiac arrhyth-

mias,and convulsions. In extreme cases, tetany of skeletal muscles

results and tetany ofthe respiratory muscles can cause death.

Part3 Integration and ControlSystems614

24. Where are the parathyroid glands located, and what

hormone do theyproduce?

25. What effect does PTH have on osteoclasts, osteoblasts, the

kidneys, the small intestine, and blood calcium and blood

phosphate levels? Whatstimulus can cause an increase in

PTH secretion?

PREDICT

A patientwith a malignant tumor had his thyroid gland removed. What

effectwould this removal have on blood levels of Ca

2

? Ifthe

parathyroid glandsare inadvertently removed along with the thyroid

gland during surgery, death can resultbecause muscles of respiration

undergo sustained contractions. Explain.

Blood Ca

(normal range)

Blood Ca

(normal range)

Blood Ca

levels increase

Blood Ca

levels decrease

Blood Ca

homeostasis

is maintained

Decreased secretion of PTH

from the parathyroid glands results.

An increase in blood Ca

levels is detected

by the cells of the parathyroid glands.

A decrease in blood Ca

levels is detected

by the cells of the parathyroid glands.

An increased secretion of PTH from

the parathyroid glands results.

• Decreased breakdown of bone by osteoclasts

results in decreased release of Ca

from bone.

• Decreased reabsorption of Ca

by the kidneys

results in increased Ca

loss in the urine.

• Decreased synthesis of active vitamin D by the

kidneys results in decreased Ca

absorption

from the small intestine.

A decrease in blood Ca

levels results because

fewer Ca

enter the blood than leave the blood.

An increase in blood Ca

levels results because

more Ca

enter the blood than leave the blood.

• Increased breakdown of bone by osteoclasts

results in increased release of Ca

from bone.

• Increased reabsorption of Ca

by the kidneys

results in decreased Ca

loss in the urine.

• Increased synthesis of active vitamin D by the

kidneys results in increased Ca

absorption

from the small intestine.

HomeostasisFigure 18.11

Regulation ofParathyroid Hormone (PTH) Secretion

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Table 18.6

Hypoparathyroidism Hyperparathyroidism

Causes

Accidental removal during Primary hyperparathyroidism: a result of abnormal parathyroid function—adenomasof the

thyroidectomy parathyroid gland (90%), hyperplasia of parathyroid idiopathic (unknown cause) cells (9%), and

carcinomas (1%)

Secondary hyperparathyroidism: caused by conditions that reduce blood Ca

2

levels, such as

inadequate Ca

2

in the diet, inadequate levels of vitamin D, pregnancy, or lactation

Symptoms

Hypocalcemia Hypercalcemia or normal blood Ca

2

levels; calcium carbonate salts may be deposited throughout

the body, especially in the renal tubules (kidney stones), lungs, blood vessels, and gastric mucosa

Normal bone structure Bones weaken and are eaten away as a result of resorption; some cases are first diagnosed when a

radiograph is taken of a broken bone

Increased neuromuscular excitability; Neuromuscular system less excitable; muscular weakness may be present

tetany, laryngospasm, and death

from asphyxiation can result

Flaccid heart muscle; cardiac Increased force of contraction of cardiac muscle; at very high blood Ca

2

levels, cardiac arrest during

arrhythmia may develop contraction is possible

Diarrhea Constipation

Causes and Symptoms of Hypersecretion and Hyposecretion of Parathyroid Hormone

Adrenal Glands

Objectives

■ Describe the structure and embryologic development of the

adrenal glands, and describe the response of the target

tissuesto each of the adrenal hormones.

■ Describe the means by which secretions of the adrenal

glandsare regulated.

Theadrenal (a˘ -dre¯na˘l)glands, also called the suprarenal

(soopra˘-re¯ na˘l) glands, are near the superior poles of the kid-

neys.Like the kidneys, they are retroperitoneal, and they are sur-

rounded by abundant adipose tissue. The adrenal glands are

enclosed by a connective tissue capsule and have a well-developed

blood supply (ﬁgure 18.12a).

The adrenal glands are composed ofan inner medulla and

an outer cortex, which are derived from two separate embry-

onic tissues.The adrenal medulla arises from neural crest cells,

which also give rise to postganglionic neurons of the sympa-

thetic division of the autonomic nervous system (see chapters

16 and 29).Unlike most glands of the body, which develop from

invaginations of epithelial tissue, the adrenal cortex is derived

from mesoderm.

Histology

Trabeculae ofthe connective tissue capsule penetrate into the adre-

nal gland in several locations, and numerous small blood vessels

course with them to supply the gland. The medulla consists of

closely packed polyhedral cells centrally located in the gland (ﬁg-

ure 18.12b). The cortex is composed of smaller cells and forms

three indistinct layers: the zona glomerulosa (glo¯ -ma¯ru¯ -lo¯ s-a˘),

the zona fasciculata (fa-siku¯-la˘-ta˘), and the zona reticularis

(re-tiku¯ -la˘ris). These three layers are functionally and struc-

turally specialized.The zona glomerulosa is immediately beneath

the capsule and is composed ofsmall clusters of cells.Beneath the

zona glomerulosa is the thickest part of the adrenal cortex, the

zona fasciculata.In this layer,the cells form long columns, or fasci-

cles,of cells that extend from the surface toward the medulla of the

gland. The deepest layer of the adrenal cortex is the zona reticu-

laris,which is a thin layer of irregularly arranged cords of cells.

Hormones ofthe Adrenal Medulla

The adrenal medulla secretes two major hormones:epinephr ine

(adrenaline; a˘-drena˘-lin), 80%, and norepinephrine (nora-

drenaline; nor-a˘-drena˘-lin),20% (table 18.7). Epinephrine and

norepinephrine are closely related to each other.In fact, norepi-

nephrine is a precursor to the formation of epinephrine. Because

the adrenal medulla consists of cells derived from the same cells

that give rise to postganglionic sympathetic neurons,its secretory

products are neurohormones.

Epinephrine and norepinephrine combine with adrenergic

receptors, which are membrane-bound receptors in target cells.

They are classiﬁed as either -adrenergic or -adrenergic recep-

tors, and each of these categories has subcategories. All of the

adrenergic receptors function through G protein mechanisms.The

-adrenergic receptors cause Ca

2

channels to open,cause the re-

lease ofCa

2

from endoplasmic reticulum by activating phospho-

lipase enzymes, open K



channels, decrease cAMP synthesis, or

stimulate the synthesis of eicosanoid molecules such as

prostaglandins.The -adrenergic receptors all increase cAMP syn-

thesis. The effects of epinephrine and norepinephrine released

from the adrenal medulla are described when the systems these

hormones affect are discussed (see chapters 16,20, 21, 24, and 26).

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Epinephrine increases blood levels of glucose. It combines

with membrane-bound receptors in the liver cells and activates

cAMP synthesis within the cells.Cyclic AMP,in turn, activates en-

zymes that catalyze the breakdown ofglycogen to glucose, thereby

causing its release into the blood. Epinephrine also increases

glycogen breakdown, the intracellular metabolism of glucose in

skeletal muscle cells,and the breakdown of fats in adipose tissue.

Epinephrine and norepinephrine increase the heart’s rate and

force of contraction and cause blood vessels to constrict in the

skin, kidneys, gastrointestinal tract,and other viscera. Also, epi-

nephrine causes dilation of blood vessels in skeletal muscles and

cardiac muscle.

Secretion ofadrenal medullary hormones prepares the indi-

vidual for physical activity and is a major component ofthe ﬁg ht-

Part3 Integration and ControlSystems616

or-ﬂight response (see chapter 16).The response results in reduced

activity in organs not essential for physical activity and in increased

blood ﬂow and metabolic activity in organs that participate in

physical activity.In addition, it mobilizes nutrients that can be

used to sustain physical exercise.

The effects ofepinephrine and norepinephrine are short-lived

because they are rapidly metabolized,excreted, or taken up by tis-

sues.Their half-life in the circulatory system is measured in minutes.

The release ofadrenal medullary hormones primarily occurs

in response to stimulation by sympathetic neurons because the ad-

renal medulla is a specialized part of the autonomic nervous sys-

tem. Several conditions, including emotional excitement,injury,

stress,exercise, and low blood glucose levels, lead to the release of

adrenal medullary neurohormones (ﬁgure 18.13).

Table 18.7

Hormones Structure Target Tissue Response

Adrenal Medulla

Epinephrine primarily; Amino acid Heart, blood vessels, Increased cardiac output; increased blood flow to skeletal muscles and

norepinephrine derivatives liver, fat cells increased blood flow to the heart (see chapter 20); increased release of glucose

and fatty acids into blood; in general, preparation for physical activity

Adrenal Cortex

Cortisol Steroid Most tissues Increased protein and fat breakdown; increased glucose production; inhibition of

immune response

Aldosterone Steroid Kidney Increased Na



reabsorption and K



and H



excretion

Sex steroids Steroids Many tissues Minor importance in males; in females, development of some secondary sexual

(primarily characteristics, such as axillary and pubic hair

androgens)

Hormones of the Adrenal Gland

Superior suprarenal artery

Adrenal gland

Abdominal aorta

Middle suprarenal artery

Inferior suprarenal artery

Renal artery

Renal vein

Fat

Kidney

Ureter

Zona

glomerulosa

Zona

fasciculata

Zona

reticularis

Connective

tissue capsule

Medulla

Cortex

LM 100x

Figure 18.12

Anatomyand Histology of the Adrenal Gland

(a) An adrenalgland is at the superior pole of each kidney. (b) The adrenalglands have an outer cortex and an inner medulla. The cortex is surrounded by a

connective tissue capsule and consistsofthree layers: the zona glomerulosa, the zona fasciculata, and the zona reticularis.

(a)

(b)

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Pheochromocytoma and Neuroblastoma

The two major disordersof the adrenal medulla are both tumors:

pheochromocytoma (fe¯o¯-kro¯mo¯-sı¯-to¯  ma˘), a benign tumor, and

neuroblastoma (nooro¯ -blas-to¯ma˘), a malignanttumor. Symptoms

resultfrom the release of large amounts of epinephrine and

norepinephrine and include hypertension (high blood pressure),

sweating, nervousness, pallor, and tachycardia (rapid heartrate). The

high blood pressure resultsfrom the effect of these hormones on the

heartand blood vessels and is correlated with an increased chance of

heartdisease and stroke.

Hormones ofthe Adrenal Cortex

The adrenal cortex secretes three hormone types:mineralocort i-

coids (miner-al-o¯-ko¯rti-koydz), glucocorticoids (gloo -ko¯-

ko¯rti-koydz), and androgens (andro¯-jenz) (see table 18.7).All

are similar in structure in that they are steroids,highly specialized

lipids that are derived from cholesterol.Because the y are lipid-

soluble, they are not stored in the adrenal gland cells but diffuse

from the cells as they are synthesized.Adrenal cortical hormones

are transported in the blood in combination with speciﬁc plasma

proteins;they are metabolized in the liver and excreted in the bile

and urine.The hormones of the adrenal cortex bind to intracellu-

lar receptors and stimulate the synthesis of speciﬁc proteins that

are responsible for producing the cell’s responses.

Mineralocorticoids

The major secretory products ofthe zona glomerulosa are the min-

eralocorticoids. Aldosterone (al-doster-o¯ n) is produced in the

greatest amounts,although other closely related mineralocorticoids

are also secreted. Aldosterone increases the rate of sodium reab-

sorption by the kidneys,thereby increasing blood levels of sodium.

Sodium reabsorption can result in increased water reabsorption by

the kidneys and an increase in blood volume providing ADH is also

secreted.Aldosterone increases K



excretion into the urine by the

kidneys,thereby decreasing blood levels of K



.It also increases the

rate ofH



excretion into the urine.When aldosterone is secreted in

high concentrations,it can result in reduced blood levels of K



and

alkalosis (elevated pH of body ﬂuids). The details of the effects of

aldosterone and the mechanisms controlling aldosterone secretion

are discussed along with kidney functions in chapters 26 and 27 and

with the cardiovascular system in chapter 21.

PREDICT

Alterationsin blood levels of sodium and potassium have profound

effectson the electrical properties of cells. Because high blood levels

ofaldosterone cause retention of sodium and excretion of potassium,

predictand explain the effects of high aldosterone levels on nerve and

muscle function. Conversely, because low blood levelsof aldosterone

cause low blood levelsof sodium and elevated blood levels of

potassium, predictthe effects of low aldosterone levels on nerve and

muscle function.

Hypothalamus

stimulated by

• Stress

• Physical activity

• Low blood glucose

levels

Increased

epinephrine and

norepinephrine

secretion

Target tissue

• Increases release of

glucose from the liver

• Increases release of fatty

acids from fat stores

• Increases heart rate

• Decreases blood flow

through blood vessels of

internal organs and

increases blood flow to

skeletal muscles and the

heart

• Decreases function of

visceral organs

• Increases blood pressure

• Increases metabolic rate in

skeletal muscles

Action potentials through

the sympathetic division

of the autonomic nervous

system

Adrenal

medulla

Figure 18.13

Regulation ofAdrenal Medullary Secretions

Stress, physicalexercise, and low blood glucose levels cause increased activityof the sympathetic nervous system, which increases epinephrine and

norepinephrine secretion from the adrenalmedulla.

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Glucocorticoids

The zona fasciculata ofthe adrenal cortex primarily secretes glu-

cocorticoid hormones, the major one of which is cortisol

(ko¯rti-sol). The target tissues and responses to the glucocorti-

coids are numerous (table 18.8).The responses are classiﬁed as

metabolic, developmental, or anti-inflammatory. Glucocorti-

coids increase fat catabolism, decrease glucose and amino acid

uptake in skeletal muscle, increase gluconeogenesis (glooko¯-

ne¯-o¯-jene˘-sis; the synthesis of g lucose from precursor molecules

like amino acids in the liver),and increase protein degradation.

Thus,some major effects of glucocorticoids are an increase in fat

Part3 Integration and ControlSystems618

and protein metabolism,blood g lucose levels,and glycogen de-

posits in cells.As a result, a reservoir of molecules that can be me-

tabolized rapidly is available to cells. Glucocorticoids are also

required for the maturation oftissues like fetal lungs and for the

development ofreceptor molecules in target tissues for epineph-

rine and norepinephrine. Glucocorticoids decrease the intensity

of the inﬂammatory response by decreasing both the number of

white blood cells and the secretion of inﬂammatory chemicals

from tissues. This anti-inflammatory effect is most important

under conditions ofstress, when the rate of glucocorticoid secre-

tion is relatively high.

Stress, hypoglycemia

CRH

Hypothalamus

pituitary

Adrenal cortex

(zona fasciculata)

Cortisol

ACTH

Target tissue

• Increases fat and protein

breakdown

• Increases blood glucose

levels

• Has anti-inflammatory

effects

1. Cortiocotropin-releasing hormone (CRH) is released from hypothalamic

neurons in response to stress or hypoglycemia and passes, by way of

the hypothalamohypophysial portal system, to the anterior pituitary.

2. In the anterior pituitary CRH binds to and stimulates cells that secrete

adrenocorticotropic hormone (ACTH).

3. ACTH binds to membrane-bound receptors on cells of the adrenal cortex

and stimulates the secretion of glucocorticoids, primarily cortisol.

4. Cortisol inhibits CRH and ACTH secretion.

Stimulatory

Inhibitory

Hypothalamohypophysial

portal system

ProcessFigure 18.14

Regulation ofCortisol Secretion

Table 18.8

Target Tissues Responses

Peripheral tissues, such as skeletal Inhibits glucose use; stimulates formation of glucose from amino acidsand, to some degree, from fats

muscle, liver, and adipose tissue (gluconeogenesis) in the liver, which results in elevated blood glucose levels; stimulates glycogen

synthesis in cells; mobilizes fats by increasing lipolysis, which results in the release of fatty acids into

the blood and an increased rate of fatty acid metabolism; increases protein breakdown and decreases

protein synthesis

Immune tissues Anti-inflammatory—depresses antibody production, white blood cell production, and the release of

inflammatory components in response to injury

Target cells for epinephrine Receptor molecules for epinephrine and norepinephrine decrease without adequate amounts of

glucocorticoid hormone

Target Tissues and Their Responses to Glucocorticoid Hormones

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ACTH is necessary to maintain the secretory activity ofthe

adrenal cortex, which rapidly atrophies without this hormone.

Corticotropin-releasing hormone (CRH) is released from the hy-

pothalamus and stimulates the anterior pituitary to secrete

ACTH.ACTH acts on the zona glomerulosa to enhance aldos-

terone secretion and on the zona fasciculata to increase cortisol

secretion. The regulation of ACTH and cortisol secretion is

outlined in ﬁgure 18.14. Both ACTH and cortisol inhibit CRH

secretion from the hypothalamus and thus constitute a negative-

feedback inﬂuence on CRH secretion.In addition, high concen-

trations ofcort isol in the blood inhibit ACTH secretion from the

anterior pituitary, and low concentrations stimulate it. This

negative-feedback loop is important in maintaining blood corti-

sol levels within a narrow range ofconcentrations. In response to

stress or hypoglycemia, blood levels of cortisol increase rapidly

because these stimuli trigger a large increase in CRH release from

the hypothalamus.Table 18.9 outlines several abnormalities asso-

ciated with hypersecretion and hyposecretion of adrenal

hormones.

PREDICT

Cortisone, a drug similar to cortisol, issometimes given to people who

have severe allergiesor extensive inﬂammation or who suffer from

autoimmune diseases. Taking thissubstance chronicallycan damage

the adrenalcortex. Explain how this damage can occur.

Adrenal Androgens

Some adrenal steroids, including androstenedione (an-dro¯-

ste¯ndı¯-o¯n), are weak androgens. They are secreted by the zona

reticularis and converted by peripheral tissues to the more po-

tent androgen,testosterone. Adrenal androgens stimulate pubic

and axillary hair growth and sexual drive in females. Their ef-

fects in males are negligible in comparison to testosterone se-

creted by the testes.Chapter 28 presents additional information

about androgens.

26. Where are the adrenal glands located? Describe the

embryonicorigin of the adrenal medulla and adrenal

cortex.

27. Name two hormones secreted by the adrenal medulla, and

listthe effects of these hormones.

28. List several conditions that can stimulate the production of

adrenal medullaryhormones. What role does the nervous

system playin the release of adrenal medullary hormones?

Howdoes this role relate to the embryonic origin of the

adrenal medulla?

29. Describe the three layers of the adrenal cortex, and name

the hormonesproduced by each layer.

30. Name the target tissue of aldosterone, and list the effects of

an increase in aldosterone secretion on the concentration of

ionsin the blood.

Table 18.9

Hyposecretion Hypersecretion

Aldosterone

Hyponatremia (low blood levels of Slight hypernatremia (high blood levels of sodium)

sodium)

Hyperkalemia (high blood levels of Hypokalemia (low blood levels of potassium)

potassium)

Acidosis Alkalosis

Low blood pressure High blood pressure

Tremors and tetany of skeletal muscles Weakness of skeletal muscles

Polyuria Acidic urine

Cortisol

Hypoglycemia (low blood glucose Hyperglycemia (high blood glucose levels; adrenal diabetes)—leads to diabetes mellitus

levels)

Depressed immune system Depressed immune system

Protein and fats from diet are unused, Destruction of tissue proteins, causing muscle atrophy and weakness, osteoporosis, weak

resulting in weight loss capillaries(easy bruising), thin skin, and impaired wound healing; mobilization and

redistribution of fats, causing depletion of fatfrom limbs and deposition in face (moon face),

neck (buffalo hump), and abdomen

Loss of appetite, nausea, and Emotional effects, including euphoria and depression

vomiting

Increased skin pigmentation (caused

byelevated ACTH)

Androgens

In women reduction of pubic and In women hirsuitism (excessive facial and body hair), acne, increased sex drive, regression of

axillary hair breast tissue, and loss of regular menses

Symptoms of Hyposecretion and Hypersecretion of Adrenal Cortex Hormones

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Clinical Focus Hormone Pathologies of the AdrenalCortex

Several pathologies are associated with

abnormal secretion of adrenal cortex

hormones.

Addison’sdisease resultsfrom abnor-

mallylow levels of aldosterone and cortisol.

The cause ofmany cases of Addison’s dis-

ease isunknown, but it is a suspected au-

toimmune disease in which the body’s

defense mechanisms inappropriately de-

stroythe adrenal cortex. Bacteria like tuber-

culosis bacteria, acquired immunodeﬁ-

ciency syndrome (AIDS), fungalinfections,

adrenal hemorrhage, and cancer can also

damage the adrenal cortex, thus causing

some cases of Addison’s disease. Pro-

longed treatment with glucocorticoids,

which suppressespituitary gland function,

can cause Addison’s disease, as can tu-

mors that damage the hypothalamus.

Symptoms of Addison’s disease include

weakness, fatigue, weight loss, anorexia,

and in manycases increased pigmentation

ofthe skin. Reduced blood pressure results

from the lossof Na



and water through the

kidney. Reduced blood pressure isthe most

criticalmanifestation and requires immedi-

ate treatment. Low blood levels of Na



high blood levelsof K



, and reduced blood

pH are consistentwith the condition.

Aldosteronism (al-doster-on-izm) is

caused by excess production of aldos-

terone. Primarya ldosteronism resultsfrom

an adrenalcortex tumor, and secondary al-

dosteronism occurswhen some extraneous

factor like overproduction of renin, a sub-

stance produced bythe kidney, increases

aldosterone secretion. Major symptoms of

aldosteronism include reduced blood lev-

elsof K



, increased blood pH, and elevated

blood pressure. Elevated blood pressure is

a resultof the retention of water and Na



the kidneys.

Cushing’ssyndrome (ﬁgure A) is a dis-

order characterized by hypersecretion of

cortisoland androgens and possibly by ex-

cess aldosterone production. The majority

ofcases are caused by excess ACTH produc-

tion by nonpituitary tumors, which usually

result from a type of lung cancer. Some

casesof increased ACTH secretion do result

from pituitary tumors. Sometimes adrenal

tumors or unidentiﬁed causes can be re-

sponsible for hypersecretion ofthe adrenal

cortexwithout increases in ACTH secretion.

Elevated secretion ofglucocorticoids results

in muscle wasting, the accumulation ofadi-

pose tissue in the face and trunk of the

body, and increased blood glucose levels.

Hypersecretion of androgens from the

adrenal cortex causes a condition called

adrenogenital (a˘ -dre¯no¯-jeni-ta˘l) syn-

drome, in which secondary sexual charac-

teristicsdevelop early in male children, and

female children are masculinized. Ifthe con-

dition developsbefore birth in females, the

external genitalia can be masculinized to

the extent that the infant’s reproductive

structures are neither clearly female nor

Figure A

Male Patientwith

Cushing’sSyndrome

male. Hypersecretion ofadrenal androgens

in male children before puberty results in

rapid and early development of the repro-

ductive system. If not treated, earlysexual

development and short stature result. The

short stature results from the effect of an-

drogenson skeletal growth (see chapter 6).

In adult females partial development of

male secondarysexual characteristics, such

asfacial hair and a masculine voice, occurs.

31. Describe the effects produced by an increase in cortisol

secretion. Starting in the hypothalamus, describe howstress

orlow blood sugar levels can stimulate cortisol release.

32. What effects do adrenal androgens have on males and

females?

Pancreas

Objectives

■ Describe the position and structure of the pancreas, and list

the substancessecreted by the pancreas and their functions.

■ Explain the regulation of insulin and glucagon secretion.

The pancreas (pankre¯-us) lies behind the peritoneum be-

tween the greater curvature of the stomach and the duodenum.It

is an elongated structure approximately 15 cm long weighing ap-

Part3 Integration and ControlSystems620

proximately 85–100 g.The head of the pancreas lies near the duo-

denum,and its body and tail extend toward the spleen.

Histology

The pancreas is both an exocrine gland and an endocrine gland.

The exocrine portion consists of acini (asi-nı¯),which produce

pancreatic juice, and a duct system,which carries the pancreatic

juice to the small intestine (see chapter 24).The endocrine par t,

consisting of pancreatic islets (islets of Langerhans), which (ﬁg-

ure 18.15) produce hormones that enter the circulatory system.

Between 500,000 and 1 million pancreatic islets are dispersed

among the ducts and acini ofthe pancreas. Each islet is composed of

alpha (␣) cells(20%), which secrete glucagon, a small polypeptide

hormone;beta (␤) cells (75%), which secrete insulin, a small pro-

tein hormone consisting oftwo polypeptide chains bound together;

Seeley−Stephens−Tate:

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III. Integration and Control

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18. Endocrine Glands

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Clinical Focus Stress

The adrenalcortex and the adrenal medulla

playmajor roles in response to stress.

In general, stressactivates nervous and

endocrine responses that prepare the body

for physicalactivity, even when physical ac-

tivityis not the most appropriate response to

the stressful conditions, such asduring an

examination or other mentallystressful situa-

tions. The endocrine response to stressin-

volves increased CRH release from the

hypothalamus and increased sympathetic

stimulation ofthe adrenal medulla. CRH stim-

ulatesACTH secretion from the anterior pitu-

itary, which in turn stimulatescortisol from

the adrenal cortex. Increased sympathetic

stimulation ofthe adrenal medulla increases

epinephrine and norepinephrine secretion.

Together, epinephrine and cortisolin-

crease blood glucose levelsand the release

of fatty acidsfrom adipose tissue and the

liver. Sympatheticinner vation ofthe pan-

creas decreasesinsulin secretion. Conse-

quently, mosttissues do not readily take up

and use glucose. Thus, glucose isavailable

primarily to the nervous system, and fatty

acidsa re used byskeletal muscle, cardiac

muscle, and other tissues.

Epinephrine and sympatheticstimula-

tion also increase cardiacoutput, increase

blood pressure, and acton the central ner-

vous system to increase alertnessand ag-

gressiveness. Cortisol also decreases the

initialinﬂammatory response.

Responses to stress illustrate the

close relationship between the nervous

and endocrine systemsand provide an ex-

ample of their integrated functions. Our

ability to respond to stressful conditions

dependson the nervous and endocrine re-

sponsesto stress.

Although responsesto stress are adap-

tive under many circumstances, they can

become harmful. For example, if stress is

chronic, the elevated secretion of cortisol

and epinephrine producesharmful effects.

Chapter 18 Endocrine Glands 621

Pancreatic duct

Pancreatic

islet

Common bile

duct from liver

Duodenum

(first part of

small intestine)

Pancreas

Exocrine portions

of pancreas (secrete

enzymes that move

through the ducts

to the small intestine)

Alpha cell

(secretes glucagon)

Beta cell

(secretes insulin)

To pancreatic

duct

To bloodstream

LM 400x

Figure 18.15

Histologyof the Pancreatic Islets

A pancreaticislet consists of clusters ofspecialized cells among the acini of the exocrine portion of the pancreas. The stain used for this slide does not distinguish

between alpha and beta cells.

Seeley−Stephens−Tate:

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18. Endocrine Glands

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and other cell types (5%).The remaining cells are either immature

cells of questionable function or delta (␦) cells, which secrete so-

matostatin,a small poly peptide hormone.Nerves from both divi-

sions of the autonomic nervous system innervate the pancreatic

islets,and a well-developed capillary network surrounds each islet.

Effectof Insulin and Glucagon

on Their TargetTissues

The pancreatic hormones play an important role in regulating the

concentration of critical nutrients in the circulatory system,espe-

cially glucose,or blood sugar, and amino acids (table 18.10). The

major target tissues ofinsulin are the liver, adipose tissue, muscles,

and the satiety center within the hypothalamus of the brain. The

satiety(sa-tı¯-e˘-t e¯) center is a collection of neurons in the hypo-

thalamus that controls appetite,but insulin doesn’t directly affect

most areas ofthe nervous system. The speciﬁc effects of insulin on

these target tissues are listed in table 18.11.

Insulin molecules bind to membrane-bound receptors on

target cells.Once insulin molecules bind their receptors, the recep-

tors cause speciﬁc proteins in the membrane to become phospho-

Part3 Integration and ControlSystems622

rylated.Part of the cells’ response to insulin is to increase the num-

ber of active-transport proteins in the membrane of cells for glu-

cose and amino acids.Finally, insulin and receptor molecules are

taken by endocytosis into the cell. The insulin molecules are re-

leased from the insulin receptors and broken down within the cell,

and the insulin receptor can once again become associated with the

plasma membrane.

In general,the target tissue response to insulin is an increase

in its ability to take up and use glucose and amino acids.Glucose

molecules that are not needed immediately as an energy source to

maintain cell metabolism are stored as glycogen in skeletal muscle,

the liver,and other tissues and are converted to fat in adipose tis-

sue.Amino acids can be broken down and used as an energy source

or to synthesize glucose,or they can be converted to protein.With-

out insulin,the ability of these tissues to take up glucose and amino

acids and use them is minimal.

The normal regulation of blood glucose levels requires in-

sulin.Blood glucose levels can increase dramatically when too little

insulin is secreted or when insulin receptors do not respond to it

(see Clinical Focus on “Diabetes Mellitus”p 623).In the absence of

insulin, the movement of glucose and amino acids into cells de-

Table 18.10

Cells In

Islets Hormone Structure Target Tissue Response

Beta () Insulin Protein Especially liver, skeletal muscle, Increased uptake and use of glucose and amino

fat tissue acid s

Alpha () Glucagon Polypeptide Liver primarily Increased breakdown of glycogen; release of glucose

into the circulatory system

Delta () Somatostatin Peptide Alpha and beta cells (some somatostatin Inhibition of insulin and glucagon secretion

isproduced in the hypothalamus)

Pancreatic Hormones

Table 18.11

Target Tissue Response to Insulin Response to Glucagon

Skeletal muscle, cardiac muscle, Increased glucose uptake and glycogen Little effect

cartilage, bone, fibroblasts, synthesis; increased uptake of

leukocytes, and mammary glands certain amino acids

Liver Increased glycogen synthesis; increased Causes rapid increase in the breakdown

use of glucose for energy (glycolysis) of glycogen to glucose (glycogenolysis)and

release of glucose into the blood

Increased formation of glucose

(gluconeogenesis) from amino acids and,

to some degree, from fats

Increased metabolism of fatty acids, resulting in

increased ketones in the blood

Adipose cells Increased glucose uptake, glycogen High concentrations cause breakdown of fats

synthesis, fat synthesis, and fatty (lipolysis); probably unimportant under most

acid uptake; increased glycolysis conditions

Nervous system Little effect except to increase glucose No effect

uptake in the satiety center

Effect of Insulin and Glucagon on Target Tissues

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Clinical Focus DiabetesMellitus

Diabetes mellitus results primarily from

inadequate secretion of insulin or the in-

ability of tissues to respond to insulin.

Insulin-dependentdiabetes mellitus (IDDM),

also called type I diabetesmellitus, affects

approximately3% of people with diabetes

mellitusand results from diminished insulin

secretion. Itdevelops as a result of autoim-

mune destruction of the pancreatic islets,

and symptoms appear after approximately

90% ofthe islets are destroyed. IDDM most

commonlydevelops in young people. Hered-

ity may play some role in the condition,

although initiation of pancreatic islet

destruction mayinvolve a viral infection of

the pancreas (see the SystemsPathology

essayp 631).

Noninsulin-dependentdiabetes melli-

tus (NIDDM), also called type II diabetes

mellitus,results from the inability of tissues

to respond to insulin. NIDDM usuallydevel-

ops in people older than 40–45 years of

age, although the age ofonset varies con-

siderably. A strong geneticcomponent ex-

ists in the disease, butits actual cause is

unknown. A peptide hormone called leptin

(see chapter 25) produced byfat cells has

been shown to decrease the response of

targettissues to insulin. It is possible that

over production of substances like this

could be responsible for NIDDM. In some

cases, abnormalreceptors for insulin or an-

tibodiesmay bind to and damage insulin re-

ceptors, or, in other cases, abnormalities

may occur in the mechanismsthat the in-

sulin receptorsactivate.

NIDDM is more common than IDDM.

Approximately97% of people who have di-

abetes mellitus have NIDDM. The reduced

number of functional receptorsfor insulin

make the uptake ofglucose by cells very

slow, which results in elevated blood glu-

cose levels after a meal. Obesity is com-

mon, although not universal, in patients

with NIDDM. Elevated blood glucose levels

cause fat cells to convert glucose to fat,

even though the rate atwhich adipose cells

take up glucose is impaired. Increased

blood glucose and increased urine produc-

tion lead to hyperosmolality of blood and

dehydration ofcells. The poor use of nutri-

ents and dehydration of cells leads to

lethargy, fatigue, and periodsof irritability.

The elevated blood glucose levels lead to

recurrent infections and prolonged wound

healing.

Patientswith NIDDM don’t suffer sud-

den, large increases in blood glucose and

severe tissue wasting because a slow rate

ofglucose uptake does occur, even though

the insulin receptorsare defective. In some

people with NIDDM, insulin production

eventually decreases because pancreatic

isletcells atrophy and IDDM develops. Ap-

proximately 25%–30% of patients with

NIDDM take insulin, 50% take oralmedica-

tion to increase insulin secretion and in-

crease the efﬁciencyof glucose utilization,

and the remainder control blood glucose

levelswith exercise and diet.

Glucose tolerance testsare used to di-

agnose diabetes mellitus. In general, the

test involves feeding the patient a large

amountof glucose after a period of fasting.

Blood samples are collected for a few

hours, and a sustained increase in blood

glucose levels strongly indicates that the

person issuffering from diabetes mellitus.

Too much insulin relative to the amount

of glucose ingested leadsto insulin shock.

The high levels of insulin cause targettis-

suesto take up glucose at a very high rate.

Asa result, blood glucose levels rapidly fall

to a low level. Because the nervoussystem

depends on glucose asits major source of

energy, neurons malfunction because ofa

lackof metabolic energy. The result is a se-

ries of nervous system responses thatin-

clude disorientation, confusion, and

convulsions. Taking too much insulin, too lit-

tle food intake after an injection ofinsulin, or

increased metabolism ofglucose due to ex-

cessexercise by a diabeticpatient can cause

insulin shock.

It appears that damage to blood ves-

selsand reduced nerve function can be re-

duced in diabetic patients suffering from

either IDDM or NIDDM bykeeping blood glu-

cose wellwithin normal levels at all times.

Doing so, however, requires increased at-

tention to diet, frequentblood glucose test-

ing, and increased chance ofsuffering from

low blood glucose levels, which leads to

symptomsof insulin shock. A strict diet and

routine exercise are often effective compo-

nents of a treatment strategy for diabetes

mellitus, and in manycases diet and exer-

cise are adequate to controlNIDDM.

Chapter 18 Endocrine Glands 623

clines dramatically, even though blood levels of these molecules

may increase to very high levels.The satiety center requires insulin

to take up glucose.In the absence of insulin, the satiety center can-

not detect the presence of glucose in the extracellular ﬂuid even

when high levels are present.The result is an intense sensation of

hunger in spite ofhigh blood glucose levels.

Blood glucose levels can fall to very low levels when too

much insulin is secreted.When too much insulin is present, target

tissues rapidly take up glucose from the blood,causing blood levels

of glucose to decline to very low levels.Although the nervous sys-

tem,except for cells of the satiety center,is not a target tissue for in-

sulin,the nervous system depends primarily on blood glucose for a

nutrient source.Consequently, low blood glucose levels cause the

central nervous system to malfunction.

Glucagon primarily inﬂuences the liver,although it has some

effect on skeletal muscle and adipose tissue (see table 18.11).

Glucagon binds to membrane-bound receptors,activates G proteins,

and increases cAMP synthesis.In general, glucagon causes the break-

down ofglycogen and increased glucose synthesis in the liver. It also

increases the breakdown of fats. The amount of glucose released

from the liver into the blood increases dramatically after glucagon

secretion increases.Because g lucagon is secreted into the hepatic

portal circulation,which carries blood from the intestine and pan-

creas to the liver,it is delivered in a relatively high concentration to

Seeley−Stephens−Tate:

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the liver,where it has its major effect. The liver also rapidly metab-

olizes it.Thus, glucagon has less of an effect on skeletal muscles and

adipose tissue than on the liver.

Regulation ofPancreatic

Hormone Secretion

Blood levels of nutrients, neural stimulation,and hormones con-

trol the secretion ofinsulin. Hyperglycemia, or elevated blood lev-

els of glucose, directly affects the beta cells and stimulates insulin

secretion. Hypoglycemia,or low blood levels of g lucose,directly

inhibits insulin secretion.Thus, blood glucose levels play a major

role in the regulation ofinsulin secretion. Certain amino acids also

stimulate insulin secretion by acting directly on the beta cells.After

a meal,when glucose and amino acid levels increase in the circula-

tory system,insulin secretion increases. During periods of fasting,

when blood glucose levels are low,the rate of insulin secretion de-

clines (ﬁgure 18.16).

The autonomic nervous system also controls insulin secre-

tion. Parasympathetic stimulation is associated with food intake,

and its stimulation acts with the elevated blood glucose levels to in-

crease insulin secretion.Sympathetic inner vation inhibits insulin

secretion and helps prevent a rapid fall in blood glucose levels.Be-

cause most tissues,except nervous tissue, require insulin to take up

glucose,sympathetic stimulation maintains blood glucose levels in

a normal range during periods of physical activity or excitement.

This response is important for maintaining normal functioning of

the nervous system.

Gastrointestinal hormones involved with the regulation of

digestion, such as gastrin, secretin, and cholecystokinin (see

chapter 24),increase insulin secretion. Somatostatin inhibits in-

sulin and glucagon secretion, but the factors that regulate so-

matostatin secretion are not clear.It can be released in response

to food intake, in which case somatostatin may prevent over-

secretion ofinsulin.

PREDICT

Explain whythe increase in insulin secretion in response to

parasympatheticstimulation and gastrointestinal hormones is

consistentwith the maintenance ofblood glucose levels in the

circulatorysystem.

Low blood glucose levels stimulate glucagon secretion,and

high blood glucose levels inhibit it.Certain amino acids and sym-

pathetic stimulation also increase glucagon secretion. After a

high-protein meal, amino acids increase both insulin and

glucagon secretion. Insulin causes target tissues to accept the

amino acids for protein synthesis, and glucagon increases the

process ofglucose synthesis from amino acids in the liver (gluco-

neogenesis).Both protein synthesis and the use of amino acids to

maintain blood glucose levels result from the low,but simultane-

ous, secretion of insulin and glucagon induced by meals high in

protein content.

33. Where is the pancreas located? Describe the exocrine and

endocrine partsof this gland and the secretions produced

byeach portion.

34. Name the target tissues for insulin and glucagon, and list

the effectsthey have on their target tissues.

35. How does insulin affect the nervous system in general and

the satietycenter in the hypothalamus in particular?

36. What effect do blood glucose levels, blood amino acid

levels, the autonomicnervous system, and somatostatin

have on insulin and glucagon secretion?

PREDICT

Compare the regulation ofglucagon and insulin secretion after a meal

high in carbohydrates, after a meallow in carbohydrates but high in

proteins, and during physicalexercise.

Hormonal Regulation ofNutrients

Objective

■ Describe how blood nutrient levels are regulated by

hormonesafter a meal and during exercise.

Two different situations—after a meal and during exercise—

can illustrate how several hormones function together to regulate

blood nutrient levels.

After a meal and under resting conditions, secretion of

glucagon,cortisol, GH, and epinephrine is reduced (ﬁgure 18.17a).

Both increasing blood glucose levels and parasympathetic stimula-

tion elevate insulin secretion to increase the uptake of glucose,

amino acids,and fats by target tissues. Substances not immediately

used for cell metabolism are stored.Glucose is converted to glyco-

gen in skeletal muscle and the liver,and is used for fat synthesis in

adipose tissue and the liver.The rapid uptake and storage of glu-

cose prevent too large an increase in blood glucose levels.Amino

acids are incorporated into proteins and fats that were ingested as

part of the meal are stored in adipose tissue and the liver.If the

meal is high in protein, a small amount of glucagon is secreted,

thereby increasing the rate at which the liver uses amino acids to

form glucose.

Within 1–2 hours after the meal,absorption of digested ma-

terials from the gastrointestinal tract declines,and blood g lucose

levels decline (ﬁgure 18.17b). As a result,secretion of g lucagon,

cortisol, GH, and epinephrine increases, thereby stimulating the

release ofg lucose from tissues.As blood glucose decreases, insulin

secretion decreases,and the rate of glucose entry into the target tis-

sues for insulin decreases. Glycogen is converted back to glucose

and is used as an energy source.Glucose is released into the blood

by the liver.The decreased uptake of glucose by most tissues, com-

bined with its release from the liver,helps maintain blood glucose

at levels necessary for normal brain function. Cells that use less

glucose start using more fats and proteins.Adipose tissue releases

fatty acids,and the liver releases triglycerides (in lipoproteins) and

ketones into the blood.Tissues take up these substances from the

Part3 Integration and ControlSystems624

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18. Endocrine Glands

Companies, 2004

Chapter 18 Endocrine Glands 625

Blood glucose

(normal range)

Blood glucose

(normal range)

Blood glucose

increases

Blood glucose

decreases

Blood glucose

homeostasis

is maintained

• Insulin stimulates the increased uptake of

glucose by most tissues (exceptions are the

brain and the liver, which do not depend on

insulin for glucose uptake).

• Excess glucose is converted to glycogen,

which is stored in skeletal muscle and liver.

• Excess glucose is converted to fat

(triglycerides) and stored in adipose tissue.

• Decreased insulin results in decreased uptake

of glucose by most tissues, which makes

glucose available for use by the brain.

• Glycogen is broken down to glucose by the

liver, which releases glucose into the blood.

• Glucose is synthesized from amino acids by

the liver, which releases glucose into the blood.

• Fat is broken down in adipose tissue, which

releases fatty acids into the blood. The use

of fatty acids by tissues spares glucose usage.

• Fatty acids are converted by the liver into

ketones, which are used by other tissues as

a source of energy.

An increase in blood glucose.

A decrease in blood glucose levels results from

the increased movement of glucose into cells.

• An increase in blood glucose is detected by

the pancreatic islet cells and results in

increased insulin secretion.

• Increased parasympathetic stimulation of the

pancreas and increased secretion of hormones

such as gastrin, secretin, and cholecystokinin

associated with digestion stimulate insulin

secretion.

A decrease in blood glucose.

An increase in blood glucose results from the

decreased movement of glucose into most tissues

and the release of glucose from the liver.

• A decrease in blood glucose is detected by

the pancreatic islet cells and results in

decreased insulin secretion.

• Increased sympathetic stimulation of the

pancreas and increased epinephrine release

from the adrenal medulla associated with

low blood glucose levels and with physical

activity inhibit insulin secretion.

HomeostasisFigure 18.16

Regulation ofInsulin Secretion

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18. Endocrine Glands

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blood and use them for energy.Fat molecules are a major source of

energy for most tissues when blood glucose levels are low.

The interactions of insulin,GH, glucagon, epinephrine, and

cortisol are excellent examples ofnegative-feedback mechanisms.

When blood glucose levels are high,these hormones cause rapid

uptake and storage of glucose,amino acids, and fats. When blood

glucose levels are low,they cause release of glucose and a switch to

fat and protein metabolism as a source ofenergy for most tissues.

Part3 Integration and ControlSystems626

During exercise,skeletal muscles require energy to support

the contraction process (see chapter 9).Although metabolism of

intracellular nutrients can sustain muscle contraction for a short

time,additional energy sources are required during prolonged ac-

tivity.Sympathetic nervous system activity, which increases during

exercise, stimulates the release of epinephrine from the adrenal

medulla and of glucagon from the pancreas (ﬁgure 18.18).These

hormones induce the conversion ofglycogen to glucose in the liver

Soon after

a meal

Circulation

Glucose

Amino acids

Fatty acids

Most cells

Take up glucose,

amino acids, and

fatty acids

The blood levels of the

following remain

relatively low:

Epinephrine

Glucagon

Growth hormone

Cortisol

Pancreas

Insulin secretion

Parasympathetic

stimulation

Several hours

after a meal

Circulation

Glucose

Amino acids

Fatty acids

Epinephrine, growth

hormone, and cortisol

secretion increase

Pancreas

Insulin secretion

Glucagon secretion

Sympathetic

stimulation

Most cells

Glucose uptake

decreases and

switch to fat

and protein

metabolism

Liver

Releases glucose,

ketones, and

triglycerides into

circulation

Adipose tissue

Releases fatty

acids into

circulation

Figure 18.17

Regulation ofBlood Nutrient Levels After a Meal

(a) Soon after a meal, glucose, amino acids, and fattyacids enter the bloodstream from the intestinaltract. Glucose and amino acids stimulate insulin secretion. In

addition, parasympatheticstimulation increases insulin secretion. Cellstake up the glucose and amino acids and use them in their metabolism. (b) Several hours

after a meal, absorption from the intestinaltract decreases, and blood levels of glucose, amino acids, and fattyacids decrease. As a result, insulin secretion

decreases, and glucagon, epinephrine, and GH secretion increase. Celluptake ofglucose decreases, and usage of fats and proteinsincreases.

(a)

(b)

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Chapter 18 Endocrine Glands 627

and the release of glucose into the blood, thus providing skeletal

muscles with a source of energy. Because epinephrine and

glucagon have short half-lives,they can rapidly adjust blood glu-

cose levels for varying conditions ofactivit y.

During sustained activity,glucose released from the liver and

other tissues is not adequate to support muscle activity,and a dan-

ger exists that blood glucose levels will become too low to support

brain function.A decrease in insulin prevents uptake of glucose by

most tissues, thus conserving glucose for the brain. Epinephrine,

glucagon,cortisol, and GH cause an increase of fatty acids, triglyc-

erides,and ketones in the blood. GH also inhibits the breakdown of

proteins,thereby preventing muscles from using themselves as an

energy source. Consequently,glucose metabolism decreases, and

fat metabolism in skeletal muscles increases.At the end of a long

race,for example, muscles rely to a large extent on fat metabolism

for energy.

37. Describe the hormonal effects after a meal that result in the

movementof nutrients into cells and their storage. Describe

the hormonal effectsthat later cause the release of stored

materialsfor use as energy.

38. During exercise, how does sympathetic nervous system

activityregulate blood glucose levels? Name ﬁve hormones

thatinteract to ensure that both the brain and muscleshave

adequate energysources.

PREDICT

Explain whylong-distance runners may nothave much of a “kick” left

when theytry to sprint to the ﬁnish line.

Hormones of the Reproductive

System

Objective

■ List the hormones secreted bythe testes and ovaries,

describe theirfunctions, and explain how they are

regulated.

Reproductive hormones are secreted primarily from the

ovaries, testes, placenta,and pituitary g land (table 18.12).These

hormones are discussed in chapter 28.The main endocrine glands

ofthe male reproductive system are the testes. The functions of the

Circulation

Epinephrine and sympathetic stimulation

also increase the breakdown of fat and the

release of fatty acids from adipose tissue.

Blood glucose levels are

maintained for normal

nervous system function.

During exercise, sympathetic

stimulation increases epinephrine and

glucagon secretion and inhibits insulin

secretion.

Epinephrine increases the rate at which

glycogen in muscle cells is used so that

the cells do not take up as much glucose

from the blood.

Short-term and prolonged exercise Exercise

Muscle

Epinephrine and glucagon

increase glycogen breakdown in

the liver, resulting in the release

of glucose into the circulatory

system.

Liver

Adipose tissue

Prolonged exercise

During prolonged exercise,

both GH and cortisol

secretion increase.

Cortisol increases protein

breakdown to amino acids

and increases glucose

synthesis from amino acids

and from some components

of fat such as glycerol.

Cortisol increases the

breakdown of fats and the

use of fatty acids as an

energy source in tissues.

GH slows the breakdown of

proteins and conserves

them.

Figure 18.18

Regulation ofBlood Nutrient Levels During Exercise

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testes depend on the secretion ofFSH and LH from the anterior pi-

tuitary gland. The main hormone secreted by the testes is testos-

terone, an androgen.Testosterone regulates the production of

sperm cells by the testes and the development and maintenance of

male reproductive organs and secondary sex characteristics.The

testes secrete another hormone called inhibin,which inhibits the

secretion ofFSH from the anterior pituitary.

The main endocrine glands of the female reproductive sys-

tem are the ovaries.Like the testes, the functions of the ovaries de-

pend on the secretion of FSH and LH from the anterior pituitary

gland.The main hormones secreted by the ovaries are estrogen and

progesterone.These hor mones,along with FSH and LH, control

the female reproductive cycle,prepare the mammar y glands for

lactation,and maintain pregnancy. Estrogen and progesterone are

also responsible for the development of the female reproductive

organs and female secondary sex characteristics. The ovaries also

secrete inhibin,which inhibits FSH secretion.

During pregnancy the ovaries and the placenta secrete es-

trogen and progesterone, which are essential to maintain preg-

nancy. In addition they secrete relaxin, which increases the

ﬂexibility of connective tissue of the symphysis pubis and helps

dilate the cervix of the uterus.This facilitates delivery by making

the birth canal larger.

39. List the hormones secreted by the testes, and give their

functions. Whathormones regulate the testes?

40. List the hormones secreted by the ovaries, and give their

functions. During pregnancy, whatother organ, in addition

to the ovaries, secreteshormones? Upon what hormones

doesovarian function depend?

Part3 Integration and ControlSystems628

Hormones of the Pineal Body

Objective

■ Describe the structure and location of the pineal body, the

productsit secretes, and the functions of these products.

Thepineal (pine¯-a˘l)bodyin the epithalamus of the brain

secretes hormones that act on the hypothalamus or the gonads to

inhibit reproductive functions. Two substances have been

proposed as secretory products: melatonin (mel-a˘-to¯nin) and

arginine vasotocin (arji-ne¯n va¯-so¯-to¯ sin, vas-o¯-tosin) (table

18.13).Melatonin can decrease GnRH secretion from the hypo-

thalamus and may inhibit reproductive functions through this

mechanism. It may also help regulate sleep cycles by increasing

the tendency to sleep.

The photoperiod is the amount of daylight and darkness

that occurs each day and changes with the seasons of the year.In

some animals,the photoperiod regulates pineal secretions (ﬁgure

18.19). For example,increased daylight initiates action potentials

in the retina ofthe eye that are propagated to the brain and cause a

decrease in the action potentials sent ﬁrst to the spinal cord and

then through sympathetic neurons to the pineal body.Decreased

pineal secretion results.In the dark, action potentials delivered by

sympathetic neurons to the pineal body increase,thereby stimulat-

ing the secretion of pineal hormones. Humans secrete larger

amounts ofmelatonin at night than in the daylight. In animals that

breed in the spring,the increased length of a day decreases pineal

secretions. Because pineal secretions inhibit reproductive func-

tions in these species,the increased length of a day results in hy-

pertrophy ofthe reproductive structures.

Table 18.12

Hormones Structure Target Tissue Response

Testis

Testosterone Steroid Most cells Aids in spermatogenesis; maintenance of functional reproductive organs; secondary sex

characteristics; sexual behavior

Inhibin Polypeptide Anterior pituitary gland Inhibits FSH secretion

Ovary

Estrogens Steroids Most cells Uterine and mammary gland development and function; external genitalia structure;

secondary sex characteristics; sexual behavior and menstrual cycle

Progesterone Steroid Most cells Uterine and mammary gland development and function; external genitalia structure;

secondary sex characteristics; menstrual cycle

Inhibin Polypeptide Anterior pituitary gland Inhibits FSH secretion

Relaxin Polypeptide Connective tissue cells Increases flexibility of connective tissue in the pelvic area, especially the symphysis pubis

Hormones of the Reproductive Organs

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Chapter 18 Endocrine Glands 629

Table 18.13

Chemical Signal Structure Target Tissue Response

PinealBody

Melatonin Amino acid At least the Inhibition of gonadotropin-releasing hormone secretion, thereby

derivative hypothalamus inhibiting reproduction; significance is not clear in humans; may help

regulate sleep–wake cycles

Arginine Amino acid Possibly the Possible inhibition of gonadotropin-releasing hormone secretion

vasotocin derivative hypothalamus

Thymus Gland

Thymosin Peptide Immune tissues Development and function of the immune system

Several Tissues (autocrine and paracrine regulatory substances)

Eicosanoids

Prostaglandins Modified fatty Most tissues Mediation of the inflammatory response increased uterine contractions;

acid ovulation, possible inhibition of progesterone synthesis; blood

coagulation; and other functions

Prostacyclins Modified fatty Most tissues Mediation of the inflammatory response and other functions

acid

Thromboxanes Modified fatty Most tissues Mediation of the inflammatory response and other functions

acid

Leukotrienes Modified fatty Most tissues Mediation of the inflammatory response and other functions

acid

Enkephalins Peptides Nervous system Reduction of pain sensation and other functions

and endorphins

Epidermal Protein Many tissues Stimulates division in many cell types and plays a role in embryonic

growth factor development

Fibroblast Protein Many tissues Stimulates cell division in many cell types and plays a role in

growth factor embryonic development

Interleukin-2 Protein Certain immune Stimulates cell division of T lymphocytes

competent cells

Other Hormones and Hormonelike Substances

Pineal

body

Postganglionic

sympathetic

neuron

Sympathetic

ganglion

Preganglionic

sympathetic

neuron

Hypothalamus

Eye

Light

rays

Neural pathways

Increasing day length reduces

neural stimulation of

melatonin secretion.

Decreasing day length

increases neural stimulation

of melatonin secretion.

Melatonin

• Inhibits GnRH secretion from hypothalamus

• May help regulate sleep cycles by enhancing

the tendency to sleep

Figure 18.19

Regulation ofMelatonin Secretion from the Pineal Body

Lightentering the eye inhibits and dark stimulates the release of melatonin from the pinealbody.

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The function of melatonin in the regulation of reproductive

functions in humans is not clear,but it is recommended by some to

enhance sleep.Because melatonin causes atrophy of reproductive

structures in some species there’s a possibility ofundesirable side

effects on the reproductive system.

The function ofthe pineal body in humans is not clear, but

tumors that destroy the pineal body correlate with early sexual

development, and tumors that result in pineal hormone secre-

tion correlate with retarded development of the reproductive

system.It’s not clear,however, if the pineal body controls the on-

set ofpuber ty.

Arginine vasotocin works with melatonin to regulate the

function ofthe reproductive system in some animals. Evidence for

the role ofmelatonin is more extensive, however.

41. Where is the pineal body located? Name the hormones it

producesand their possible effects.

Hormones of the Thymus

Thethymus (thı¯mu˘s) is in the neck and superior to the heart in

the thorax, and it secretes a hormone called thymosin (thı¯mo¯-

sin) (see table 18.13).Both the thymus and thymosin play an im-

portant role in the development of the immune system and are

discussed in chapter 22.

Hormones of the

GastrointestinalTract

Several hormones are released from the gastrointestinal tract.They

regulate digestive functions by inﬂuencing the activity ofthe stom-

ach,intestines, liver,and pancreas. They are discussed in chapter 24.

Hormonelike Substances

Objective

■ Deﬁne and give examples of autocrine and paracrine

chemical signalsin the body.

Autocrine chemical signalsare released from cells that in-

fluence the same cell type from which they are released.

Paracrine chemical signals are released from one cell type, dif-

fuse short distances, and inﬂuence the activity of another cell

type,which is its target tissue. Autocrine and paracrine chemical

signals differ from hormones in that they are not secreted from

discrete endocrine glands,they have local effects rather than sys-

temic effects,or they have functions that are not understood ade-

quately to explain their role in the body.Examples of autocrine

chemical signals include chemical mediators ofinﬂammation de-

rived from the fatty acid arachidonic(a˘-rak-i-donik)acid, such

as eicosanoids and modiﬁed phospholipids.The eicosanoids in-

clude prostaglandins (prossta˘-glandinz), thromboxanes

(thrombok-za¯ nz), prostacyclins (pros-ta˘-sı¯klinz),and leuko-

trienes(looko¯-trı¯e¯nz). Modiﬁed phospholipids include platelet

Part3 Integration and ControlSystems630

activating factor (see chapter 19).Paracrine chemical signals in-

clude substances that play a role in modulating the sensation of

pain, such as endorphins (endo¯r-ﬁnz) and enkephalins(en-

kefa˘-linz),and several peptide growth factors, such as epidermal

growth factor,ﬁbroblast growth factor, and interleukin-2 (in-

ter-lookin) (see table 18.13).

Prostaglandins, thromboxanes, prostacyclins, and leuko-

trienes are released from injured cells and are responsible for initi-

ating some of the symptoms of inﬂammation (see chapter 22), in

addition to being released from certain healthy cells.For example,

prostaglandins are involved in the regulation of uterine contrac-

tions during menstruation and childbirth, the process of ovula-

tion, the inhibition of progesterone synthesis by the corpus

luteum,the regulation of coagulation, kidney function, and modi-

ﬁcation ofthe effect of other hormones on their target tissues. Pain

receptors are stimulated directly by prostaglandins and other

inﬂammatory compounds,or prostaglandins cause vasodilation of

blood vessels, which is associated with headaches. Anti-

inﬂammatory drugs like aspirin inhibit prostaglandin synthesis

and,as a result, reduce inﬂammation and pain. These examples are

paracrine regulatory substances because they are synthesized and

secreted by the cells near their target cells.Once prostaglandins en-

ter the circulatory system,they are metabolized rapidly.

Three classes of peptide molecules, which are endogenously

produced on analgesics, bind to the same receptor molecules as

morphine.They include enkephalins, endorphins, and dynorphins

(dı¯no¯ r-ﬁnz).They are produced in several sites in the body, such as

parts ofthe brain, pituitary, spinal cord, and gut. They act as neuro-

transmitters in some neurons of both the central and peripheral

nervous systems and as hormones or paracrine regulatory sub-

stances.In general, they moderate the sensation of pain (see chapter

14). Decreased sensitivity to painful stimuli during exercise and

stress may result from the increased secretion ofthese substances.

Several proteins can be classiﬁed as growth factors.They gen-

erally function as paracrine chemical signals because they are se-

creted near their target tissues.Epidermal growth factor stimulates

cell divisions in a number oftissues and plays an important role in

embryonic development.Interleukin-2 stimulates the proliferation

of T lymphocytes and plays a very important role in immune re-

sponses (see chapter 22).The number of hormonelike substances in

the body is large,and only a few of them have been mentioned here.

Chemical communication among cells in the body is complex,well

developed,and necessary for maintenance of homeostasis. Investi-

gations into chemical regulation increase our knowledge of body

functions—knowledge that can be used in the development of

techniques for the treatment ofpathologic conditions.

42. Deﬁne autocrine chemical signals. List eicosanoids and

modiﬁed phospholipidsthat function as autocrine chemical

signals, and explain theirfunction.

43. Deﬁne paracrine chemical signals. List examples of

substancesthat play a role in modulating pain or are

peptide growth factors. Howcan prostaglandins function as

both autocrine and paracrine chemical signals?

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Figure B

A 10-Year-Old BoyGiving HimselfInsulin

Insulin-Dependent Diabetes Mellitus

Systems Pathology

Billy, a 10-year-old boy, wasdiagnosed as having insulin-dependent

diabetesmellitus (IDDM). Billy’s mother took him to a physician after

noticing thathe was constantly hungry and was losing weight rapidly

in spite of hisunusually large food intake. More careful observation

made itclear that Billy was constantly thirsty and that he urinated fre-

quently. In addition, he feltweak and lethargic, and his breath occa-

sionally had a distinctive sweet, or acetone, odor. Diagnostictests

conﬁrmed thathe had IDDM.

Background Information

IDDM is caused by diminished insulin secretion. In patients with

IDDM, nutrients are absorbed from the intestine after a meal, but

skeletalmuscle, adipose tissue, and other target tissues don’t readily

take glucose into their cells, and liver cellscannot convert glucose to

glycogen. Consequently, blood levelsofglucose increase dramatically.

Glucagon and glucocorticoid secretion increase because the glucose

in the blood cannotenter the cells that produce these hormones, so

their rate ofsecretion is similar to when blood glucose levels are low.

Epinephrine secretion also increases. In response to these hormones,

glycogen, fats, and proteinsare broken down and metabolized to pro-

duce the ATP required bycells.

When blood glucose levelsare very high, glucose is excreted in

the urine, which resultsin an increase in urine volume. The rapid loss

of water in the urine increases the osmotic concentration ofblood,

which increasesthe sensation of thirst. The increased osmolality of

blood and the ionicimbalances caused by the loss of Ca

2

and K



the large amountof urine produced cause neurons to malfunction and

result in diabetic coma in severe cases. When insulin levelsin the

blood are low and cellsof the nervous system that controlappetite ap-

pear to be unable to take up glucose even when blood glucose levels

are high, the resultis an increased appetite. Polyuria (pol-e¯-u¯ re¯-a˘; in-

creased urine volume), polydipsia(pol-e¯-dipse¯-a˘; increased thirst),

and polyphagia (pol-e¯-fa¯je¯-a˘; increased appetite) are major symp-

toms of IDDM. Acidosisis caused by rapid fat catabolism, which re-

sultsin increased levels of acetoacetic (ase-to¯-a-se¯tik)acid, which is

converted to acetone (ase-to¯n) and ␤-hydroxybutyric (ba¯ta˘ hı¯-

drokse¯-bu¯ -tirik) acid. These three substances collectively are re-

ferred to asketone (ke¯ to¯n)bodies. The presence of excreted ketone

bodiesin the urine and in expired air (“acetone breath”) suggests that

the person hasdiabetes mellitus.

Billy’sphysician explained that prior to the late 1920s people

with hiscondition always died in a relatively short time. They suffered

from massive weightloss and appeared to starve to death in spite of

eating a large amountof food. The physician explained thatbecause of

Chapter 18 Endocrine Glands 631

the discoveryof insulin, many people with his type of diabetes melli-

tusare able to live nearly normal lives. Taking insulin injections(ﬁgure

B), monitoring blood glucose levels, and following a strictdiet to keep

blood glucose levels within a normalrange of values are the major

treatmentsfor IDDM.

PREDICT

After Billywas diagnosed with diabetes mellitus, he followed a strict

dietand took insulin for a few months. He began to feel much better

than before. In fact, he feltso well that he began to sneakcandy and

softdrinks when his parents were not around. Predict the

consequencesof his actionson his health.

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System Interactions

System Interaction

Muscular Untreated diabetes mellitus, especially IDDM, results in severe muscle atrophy because glycogen, stored fat, and proteins of muscles

are broken down and used asenergy sources. Ionic imbalances can also lead to muscular weakness.

Nervous Untreated IDDM can have dramatic effects on the nervous system. When the blood glucose reaches very high levels, the osmolality

of the extracellular fluid is increased. Thus, water diffuses from the neurons of the brain. In addition, acidosisdevelops because

of the rapid metabolism of fats. As a result, the nervous system cannot function normally, and diabetic coma can result. A long-term

effect is the degeneration of the myelin sheaths of neurons, resulting in abnormal nerve functions.

Cardiovascular Atherosclerosis develops more rapidly in diabetics than in the healthy population. Changes in the capillary structure and high

blood glucose levels increase the probability of reduced circulation and gangrene.

Lymphatic and The tendency to develop infections increases, and the rate of healing is slower. In some cases, an allergic reaction to the injected

immune insulin occurs.

Respiratory Acidosis causes hyperventilation, which increases blood pH back toward normal levels by decreasing blood CO

levels.

Urinary High blood glucose levels cause polyuria, the urine contains glucose and has a high osmolality, and people with diabetes

are more likely to develop urinary tract infections.

Reproductive Pregnant women with diabetes mellitus may have babies with a larger-than-normal birth weight because the blood glucose levels

may be high in the mother and fetus, and the fetus’s pancreas produces insulin. Glucose is therefore taken up by cells of the

fetus, where it is converted to fat.

Effect of IDDM on Other Systems

Part3 Integration and ControlSystems632

Effects of Aging on the Endocrine

System

Objective

■ Describe the effects of aging on the endocrine system.

Age-related changes in the endocrine system are not the

same for all of the endocrine glands. There’s a gradual decrease in

the secretory activity of some endocrine glands, but not in all of

them. In addition, some decreases in secretory activity of en-

docrine glands appear to be secondary to a decrease in physical ac-

tivity as people age.

There is a decrease in the secretion ofGH as people age. The

decrease is greater in people who do not exercise,and it may not

occur in people who exercise regularly.Decreasing GH secretion

may explain the gradual decrease in lean body mass.For example,

bone mass and muscle mass decrease as GH levels decline.At the

same time adipose tissue increases.

Melatonin secretion decreases in aging people. The de-

crease may inﬂuence age-related changes in sleep patterns and

the secretory patterns of other hormones such as GH and

testosterone.

The secretion of thyroid hormones decreases slightly with

increasing age,and there’s a decrease in the T

ratio.This may

be less of a decrease in the secretory activity of the thyroid gland

than it is compensating for the decrease in the lean body mass in

aging people.Age-related damage to the thyroid gland by the im-

mune system can occur.This change occurs in women more than

in men. The result is that approximately 10% of elderly women

have thyroid glands that don’t produce enough T

and T

Parathyroid hormone secretion doesn’t appear to decrease

with age.Blood levels of Ca

2

may decrease slightly because ofre-

duced dietary calcium intake and vitamin D levels. The greatest

risk is a loss of bone matrix as parathyroid hormone increases to

maintain blood levels ofCa

2

within their normal range.

The kidneys of the elderly secrete less renin. Consequently,

there’s a reduced ability to respond to decreases in blood pressure

by activating the renin-angiotensin-aldosterone mechanism (see

chapter 26).

Reproductive hormone secretion gradually declines in el-

derly men,and women experience menopause. These age-related

changes are described in chapter 28.

There are no age-related decreases in the ability to regulate

blood glucose levels. However,there’s an age-related tendency to

develop type II diabetes for those who have a familial tendency to

do so,and it is correlated with age-related increases in body weight.

Thymosin from the thymus decreases with age.Fewer imma-

ture lymphocytes are able to mature and become functional,and

the immune system becomes less effective in protecting the body.

There’s an increased susceptibility to infection and to cancer.

44. Describe age-related changes in the secretion and the

consequencesof these changes in the following: GH,

melatonin, thyroid hormones, renin, and reproductive

hormones. Name one hormone thatdoesn’t appear to

decrease with age.

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Chapter 18 Endocrine Glands 633

Functionsof the Endocrine System

(p. 598)

Main regulatory functions include water balance,uterine contractions and

milk release,metabolism and tissue maturation, ion regulation, heart rate

and blood pressure regulation,control of blood glucose and other nutri-

ents,immune system regulation, and control of reproductive functions.

PituitaryGland and Hypothalamus

(p. 598)

1. The pituitary gland secretes at least nine hormones that regulate

numerous body functions and other endocrine glands.

2. The hypothalamus regulates pituitary gland activity through

neurohormones and action potentials.

Structure ofthe Pituitary Gland

1. The posterior pituitary develops from the ﬂoor of the brain and

consists ofthe infundibulum and pars nervosa.

2. The anterior pituitary develops from the roof of the mouth and

consists ofthe pars distalis, pars intermedia, and pars tuberalis.

Relationship ofthe Pituitary to the Brain

1. The hypothalamohypophysial portal system connects the

hypothalamus and the anterior pituitary.

• Neurohormones are produced in hypothalamic neurons.

• Through the portal system, the neurohormones inhibit or

stimulate hormone production in the anterior pituitary.

2. The hypothalamohypophysial tract connects the hypothalamus and

the posterior pituitary.

• Neurohormones are produced in hypothalamic neurons.

• The neurohormones move down the axons of the nerve tract and

are secreted from the posterior pituitary.

Hormonesof the Pituitary Gland

(p. 601)

Posterior PituitaryHormones

1. ADH promotes water retention by the kidneys.

2. Oxytocin promotes uterine contractions during delivery and causes

milk ejection in lactating women.

Anterior PituitaryHormones

1. GH,or somatotropin

• GH stimulates the uptake of amino acids and their conversion into

proteins and stimulates the breakdown offats and glycogen.

• GH stimulates the production of somatomedins; together they

promote bone and cartilage growth.

• GH secretion increases in response to an increase in blood amino

acids,low blood glucose, or stress.

• GH is regulated by GHRH and GHIH, or somatostatin.

2. TSH,or thyrotropin, causes the release of thyroid hormones.

3. ACTH is derived from proopiomelanocortin;it stimulates cortisol

secretion from the adrenal cortex and increases skin pigmentation.

4. Several hormones in addition to ACTH are derived from

proopiomelanocortin.

• Lipotropins cause fat breakdown.

•  endorphins play a role in analgesia.

• MSH increases skin pigmentation.

5. LH and FSH

• Both hormones regulate the production of gametes and

reproductive hormones (testosterone in males;estrogen and

progesterone in females).

• GnRH from the hypothalamus stimulates LH and FSH secretion.

6. Prolactin stimulates milk production in lactating females.Prolactin-

releasing hormone and prolactin-inhibiting hormone from the

hypothalamus affect prolactin secretion.

SUMMARY

Thyroid Gland

(p. 607)

The thyroid gland is just inferior to the larynx.

Histology

1. The thyroid gland is composed of small,hollow balls of cells called

follicles,which contain thyroglobulin.

2. Parafollicular cells are scattered throughout the thyroid gland.

Thyroid Hormones

1. Thyroid hormone synthesis

• Iodide ions are taken into the follicles by active transport,are

oxidized,and are bound to tyrosine molecules in thyroglobulin.

• Thyroglobulin is secreted into the follicle lumen.Tyrosine

molecules with iodine combine to form T

and T

,thyroid

hormones.

• Thyroglobulin is taken into the follicular cells and is broken down;

and T

diffuse from the follicles to the blood.

2. Thyroid hormone transport in the blood

•T

and T

bind to thyroxine-binding globulin and other plasma

proteins.

• The plasma proteins prolong the half-life of T

and T

and

regulate the levels ofT

and T

in the blood.

• Approximately one-third of the T

is converted into functional T

3. Mechanism of action of thyroid hormones

• Thyroid hormones bind with intracellular receptor molecules and

initiate new protein synthesis.

4. Effects of thyroid hormones

• Thyroid hormones increase the rate of glucose, fat, and protein

metabolism in many tissues,thus increasing body temperature.

• Normal growth of many tissues is dependent on thyroid

hormones.

5. Regulation of thyroid hormone secretion

• Increased TSH from the anterior pituitary increases thyroid

hormone secretion.

• TRH from the hypothalamus increases TSH secretion.TRH

increases as a result ofchronic exposure to cold, food deprivation,

and stress.

•T

and T

inhibit TSH and TRH secretion.

Calcitonin

1. The parafollicular cells secrete calcitonin.

2. An increase in blood calcium levels stimulates calcitonin secretion.

3. Calcitonin decreases blood calcium and phosphate levels by

inhibiting osteoclasts.

Parathyroid Glands

(p. 613)

1. The parathyroid glands are embedded in the thyroid glands.

2. PTH increases blood calcium levels.

• PTH stimulates osteoclasts.

• PTH promotes calcium reabsorption by the kidneys and the

formation ofactive vitamin D by the kidneys.

• Active vitamin D increases calcium absorption by the intestine.

3. A decrease in blood calcium levels stimulates PTH secretion.

AdrenalGlands

(p. 615)

1. The adrenal glands are near the superior poles of the kidneys.

2. The adrenal medulla arises from neural crest cells and functions as

part ofthe sympathetic ner vous system.The adrenal cortex is

derived from mesoderm.

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3. Histology

• The medulla is composed of closely packed cells.

• The cortex is divided into three layers:the zona glomer ulosa,the

zona fasciculata,and the zona reticularis.

4. Hormones of the adrenal medulla

• Epinephrine accounts for 80% and norepinephrine for 20% of the

adrenal medulla hormones.

• Epinephrine increases blood glucose levels, use of glycogen and

glucose by skeletal muscle,and heart rate and force of

contraction,and it causes vasoconstriction in the skin and

viscera and vasodilation in skeletal and cardiac muscle.

• Norepinephrine stimulates cardiac muscle and causes

constriction ofmost peripheral blood vessels.

• The adrenal medulla hormones prepare the body for physical

activity.

• Release of adrenal medulla hormones is mediated by the

sympathetic nervous system in response to emotions,injury,

stress,exercise, and low blood glucose levels.

5. Hormones of the adrenal cortex

• The zona glomerulosa secretes the mineralocorticoids, especially

aldosterone.Aldosterone acts on the kidneys to increase sodium

and to decrease potassium and hydrogen levels in the blood.

• The zona fasciculata secretes glucocorticoids,especially cortisol.

• Cortisol increases fat and protein breakdown, increases glucose

synthesis from amino acids,decreases the inﬂammatory

response,and is necessary for the development of some tissues.

• ACTH from the anterior pituitary stimulates cortisol secretion.

CRH from the hypothalamus stimulates ACTH release.Low

blood glucose levels or stress stimulate CRH secretion.

• The zona reticularis secretes androgens.In females, androgens

stimulate axillary and pubic hair growth and sexual drive.

Pancreas

(p. 620)

1. The pancreas is located along the small intestine and the stomach.It

is both an exocrine and an endocrine gland.

2. Histology

• The exocrine portion of the pancreas consists of a complex duct

system that ends in small sacs called acini that produce pancreatic

digestive juices.

• The endocrine portion consists of the pancreatic islets. Each islet is

composed ofalpha cells, which secrete glucagon, beta cells, which

secrete insulin,and delta cells, which secrete somatostatin.

3. Effect of insulin on its target tissues

• Insulin’s target tissues are the liver,adipose tissue, muscle,and the

satiety center in the hypothalamus.The nervous system is not a

target tissue,but it does rely on blood glucose levels maintained by

insulin.

• Insulin increases the uptake of glucose and amino acids by cells.

Glucose is used for energy or is stored as glycogen.Amino acids

are used for energy or are converted to glucose or proteins.

4. Effect of glucagon on its target tissue

• Glucagon’s target tissue is mainly the liver.

• Glucagon causes the breakdown of glycogen and fats for use as an

energy source.

5. Regulation of pancreatic hormone secretion

• Insulin secretion increases because of elevated blood glucose

levels,an increase in some amino acids, parasympathetic

stimulation,and gastrointestinal hormones. Sympathetic

stimulation decreases insulin secretion.

• Glucagon secretion is stimulated by low blood glucose levels,

certain amino acids,and sympathetic stimulation.

• Somatostatin inhibits insulin and glucagon secretion.

HormonalRegulation of Nutrients

(p. 624)

1. After a meal,the following events take place:

• High glucose levels inhibit glucagon, cortisol, GH,and

epinephrine,which reduces the release of glucose from tissues.

• Insulin secretion increases as a result of the high blood glucose

levels,thereby increasing the uptake of glucose, amino acids, and

fats,which are used for energy or are stored.

• Sometime after the meal, blood glucose levels drop.Glucagon,

cortisol,GH, and epinephrine levels increase, insulin levels

decrease,and glucose is released from tissues.

• Adipose tissue releases fatty acids, triacylglycerols,and ketones,

which most tissues use for energy.

2. During exercise the following events occur:

• Sympathetic activity increases epinephrine and glucagon

secretion,causing a release of glucose into the blood.

• Low blood sugar levels, caused by uptake of glucose by skeletal

muscles,stimulate epinephrine, glucagon, GH, and cortisol

secretion,causing an increase in fatty acids, triacylglycerols, and

ketones in the blood,all of which are used for energy.

Hormonesof the Reproductive System

(p. 627)

The ovaries, testes,placenta, and pituitary gland secrete reproductive

hormones.

Hormonesof the Pineal Body

(p. 628)

The pineal body produces melatonin and arginine vasotocin,which can

inhibit reproductive maturation and may regulate sleep–wake cycles.

Hormonesof the Thymus

(p. 630)

The thymus gland produces thymosin,which is involved in the develop-

ment ofthe immune system.

Hormonesof the Gastrointestinal Tract

(p. 630)

The gastrointestinal tract produces several hormones that regulate diges-

tive functions.

Hormonelike Substances

(p. 630)

1. Autocrine and paracrine chemical signals are produced by many

cells ofthe body and usually have a local effect. They affect many

body functions.

2. Eicosanoids such as prostaglandins,prostacyclins, thromboxanes,

and leukotrienes are derived from fatty acids and mediate

inﬂammation and other functions.Endorphins, enkephalins, and

dynorphins are analgesic substances.Growth factors inﬂuence cell

division and growth in many tissues,and interleukin-2 inﬂuences

cell division in T cells ofthe immune system.

Effectsof Aging on the Endocrine System

(p. 632)

There is a gradual decrease in the secretion rate ofmost, but not all, hor-

mones. Some decreases are secondary to gradual decreases in physical

activity.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

18. Endocrine Glands

Companies, 2004

Chapter 18 Endocrine Glands 635

1. The pituitary gland

a. develops from the ﬂoor of the brain.

b. develops from the roofof the mouth.

c. is stimulated by neurohormones produced in the midbrain.

d. secretes only three major hormones.

e. both a and b.

2. The hypothalamohypophysial portal system

a. contains one capillary bed.

b. carries hormones from the anterior pituitary to the body.

c. carries hormones from the posterior pituitary to the body.

d. carries hormones from the hypothalamus to the anterior pituitary.

e. carries hormones from the hypothalamus to the posterior

pituitary.

3. Which of these hormones is not a hormone that is secreted into the

hypothalamohypophysial portal system?

a. GHRH

b. TRH

c. PIH

d. GnRH

e. ACTH

4. Hormones secreted from the posterior pituitary

a. are produced in the anterior pituitary.

b. are transported to the posterior pituitary within axons.

c. include GH and TSH.

d. are steroids.

e. all of the above.

5. Which ofthese stimulates the secretion of ADH?

a. elevated blood osmolality

b. decreased blood osmolality

c. releasing hormones from the hypothalamus

d. ACTH

e. increased blood pressure

6. Oxytocin is responsible for

a. preventing milk release from the mammary glands.

b. preventing goiter.

c. causing contraction of the uterus.

d. maintaining normal calcium levels.

e. increasing metabolic rate.

7. Growth hormone

a. increases the usage of glucose.

b. increases the breakdown oflipids.

c. decreases the synthesis of proteins.

d. decreases the synthesis ofglycogen.

e. all of the above.

8. Which of these hormones stimulates somatomedin secretion?

a. FSH

b. GH

c. LH

d. Prolactin

e. TSH

9. Hypersecretion of growth hormone

a. results in giantism if it occurs in children.

b. causes acromegaly in adults.

c. increases the probability that one will develop diabetes.

d. can lead to severe atherosclerosis.

e. all of the above.

10. LH and FSH

a. are produced in the hypothalamus.

b. production is increased by TSH.

c. promote the production of gametes and reproductive hormones.

d. inhibit the production ofprolactin.

e. all of the above.

11. Thyroid hormones

a. require iodine for their production.

b. are made from the amino acid tyrosine.

c. are transported in the blood bound to thyroxine-binding

globulin.

d. all ofthe above.

12. Which of these symptoms is associated with hyposecretion of the

thyroid gland?

a. hypertension

b. nervousness

c. diarrhea

d. weight loss with a normal or increased food intake

e. decreased metabolic rate

13. Which of these conditions most likely occurs ifa healthy person

receives an injection ofthyroid hormone?

a. The secretion rate of TSH declines.

b. The person develops symptoms ofhypothyroidism.

c. The person develops hypercalcemia.

d. The person secretes more TRH.

14. Which of these occurs as a response to a thyroidectomy (removal of

the thyroid gland)?

a. increased calcitonin secretion

b. increased T

and T

secretion

c. decreased TRH secretion

d. increased TSH secretion

15. Choose the statement that most accurately predicts the long-term

effect ofa substance that prevents active transport of iodide by the

thyroid gland.

a. Large amounts of thyroid hormone accumulate within the

thyroid follicles,but little is released.

b. The person exhibits hypothyroidism.

c. The anterior pituitary secretes smaller amounts of TSH.

d. The circulating levels ofT

and T

increase.

16. Calcitonin

a. is secreted by the parathyroid glands.

b. levels increase when blood calcium levels decrease.

c. causes blood calcium levels to decrease.

d. insufﬁciency results in weak bones and tetany.

17. Parathyroid hormone secretion increases in response to

a. a decrease in blood calcium levels.

b. increased production ofparathyroid-stimulating hormone from

the anterior pituitary.

c. increased secretion of parathyroid-releasing hormone from the

hypothalamus.

d. increased secretion ofcalcitonin.

e. a decrease in secretion of ACTH.

18. If parathyroid hormone levels increase,which of these conditions is

expected?

a. Osteoclast activity is increased.

b. Calcium absorption from the small intestine is inhibited.

c. Calcium reabsorption from the urine is inhibited.

d. Less active vitamin D is formed in the kidneys.

e. All of the above.

19. The adrenal medulla

a. produces steroids.

b. has cortisol as its major secretory product.

c. decreases its secretions during exercise.

d. is formed from a modiﬁed portion ofthe sympathetic division of

the ANS.

e. all of the above.

REVIEW AND COMPREHENSION

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

18. Endocrine Glands

Companies, 2004

Part3 Integration and ControlSystems636

20. Pheochromocytoma is a condition in which a benign tumor results

in hypersecretion ofthe adrenal medulla. The symptoms that one

would expect include

a. hypotension.

b. bradycardia.

c. pallor (decreased blood ﬂow to the skin).

d. lethargy.

e. hypoglycemia.

21. Which of these is not a hormone secreted by the adrenal cortex?

a. aldosterone

b. androgens

c. cortisol

d. epinephrine

22. If aldosterone secretions increase

a. blood potassium levels increase.

b. blood hydrogen levels increase.

c. acidosis results.

d. blood sodium levels decrease.

e. blood volume increases.

23. Glucocorticoids (cortisol)

a. increase the breakdown of fats.

b. increase the breakdown ofproteins.

c. increase blood glucose levels.

d. decrease inﬂammation.

e. all of the above.

24. The release of cortisol from the adrenal cortex is regulated by other

hormones.Which of these hormones is correctly matched with its

origin and function?

a. CRH—secreted by the hypothalamus;stimulates the adrenal

cortex to secrete cortisol

b. CRH—secreted by the anterior pituitary;stimulates the adrenal

cortex to secrete cortisol

c. ACTH—secreted by the hypothalamus;stimulates the adrenal

cortex to secrete cortisol

d. ACTH—secreted by the anterior pituitary;stimulates the

adrenal cortex to produce cortisol

25. Which ofthese would be expected in Cushing’s syndrome?

a. loss of hair in women

b. deposition offat in the face, neck, and abdomen

c. low blood glucose

d. low blood pressure

e. all of the above

26. Within the pancreas,the pancreatic islets produce

a. insulin.

b. glucagon.

c. digestive enzymes.

d. both a and b.

e. all of the above.

27. Insulin increases

a. the uptake of glucose by its target tissues.

b. the breakdown ofprotein.

c. the breakdown of fats.

d. glycogen breakdown in the liver.

e. all of the above.

28. Which of these tissues is least affected by insulin?

a. adipose tissue

b. heart

c. skeletal muscle

d. brain

e. liver

29. Glucagon

a. primarily affects the liver.

b. causes glycogen to be stored.

c. causes blood glucose levels to decrease.

d. decreases fat metabolism.

e. all of the above.

30. When blood glucose levels increase,the secretion of which of these

hormones increases?

a. glucagon

b. insulin

c. GH

d. cortisol

e. epinephrine

31. If a person who has diabetes mellitus forgot to take an insulin

injection,symptoms that may soon appear include

a. acidosis.

b. hyperglycemia.

c. increased urine production.

d. lethargy and fatigue.

e. all of the above.

32. Which of these is not a hormone produced by the ovaries?

a. estrogen

b. progesterone

c. prolactin

d. inhibin

e. relaxin

33. Melatonin

a. is produced by the posterior pituitary.

b. production increases as day length increases.

c. inhibits the development of the reproductive system.

d. increases GnRH secretion from the hypothalamus.

e. decreases the tendency to sleep.

34. Which of these substances,produced by many tissues of the body,

can promote inﬂammation,pain, and vasodilation of blood vessels?

a. endorphin

b. enkephalin

c. thymosin

d. epidermal growth factor

e. prostaglandin

35. Which of the changes listed does notdecrease with ag ing of the

endocrine system?

a. GH secretion

b. melatonin secretion

c. thyroid hormone secretion

d. parathyroid hormone secretion

e. renin secretion by the kidneys

Answers in Appendix F

CRITICAL THINKING

1. The hypothalamohypophysial portal system connects the

hypothalamus with the anterior pituitary.Why is such a special

circulatory system advantageous?

2. The secretion of ADH can be affected by exposure to hot or cold

environmental temperatures.Predict the effect of a hot environment

on ADH secretion,and explain why it is advantageous. Propose a

mechanism by which temperature produces a change in ADH

secretion.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

18. Endocrine Glands

Companies, 2004

Chapter 18 Endocrine Glands 637

3. A patient exhibits polydipsia (thirst),polyuria (excess urine

production),and urine with a low speciﬁc gravity (contains few ions

and no glucose).If you want to reverse the symptoms, would you

administer insulin,glucagon, ADH, or aldosterone? Explain.

4. A patient complains of headaches and visual disturbances.A casual

glance reveals that the patient’s ﬁnger bones are enlarged in diameter,

a heavy deposition ofbone exists over the eyes, and the patient has a

prominent jaw.The doctor tells you that the headaches and visual

disturbances result from increased pressure within the skull and that

the patient is suffering from a pituitary tumor that is affecting

hormone secretion.Name the hormone that is causing the problem,

and explain why an increase in pressure exists within the skull.

5. Most laboratories have the ability to determine blood levels ofTSH,

,and T

.Given that ability, design a method of determining

whether hyperthyroidism in a patient results from a pituitary

abnormality or from the production ofa nonpituitary thyroid

stimulatory substance.

6. An anatomy and physiology instructor asks two students to predict

a patient’s response to chronic vitamin D deﬁciency.One student

claims that the person would suffer from hypocalcemia and the

symptoms associated with that condition.The other student claims

that calcium levels would remain within their normal range,

although at the low end ofthe range, and that bone resorption

would occur to the point that advanced osteomalacia might be seen.

With whom do you agree,and why?

7. Given the ability to measure blood glucose levels,design an

experiment that distinguishes between a person with diabetes,a

healthy person,and a person who has a pancreatic tumor that

secretes large amounts ofinsulin.

8. A patient arrives in an unconscious condition.A medical emergency

bracelet reveals that he has diabetes.The patient can be in diabetic

coma or insulin shock.How could you tell which,and what

treatment would you recommend for each condition?

9. Diabetes mellitus can result from a lack ofinsulin, which results in

hyperglycemia.Adrenal diabetes and pituitary diabetes also produce

hyperglycemia.What hormones produce the last two conditions?

10. Predict some of the consequences of exposure to intense and

prolonged stress.

Answers in Appendix G

ANSWERS TO PREDICT QUESTIONS

1. The cell bodies of the neurosecretory cells that produce ADH are in

the hypothalamus,and their axons extend into the posterior

pituitary,where ADH is stored and secreted.Removing the posterior

pituitary severs the axons,resulting in a temporary reduction in

secretion.The cell bodies still produce ADH, however,and as the

ADH accumulates at the ends ofsevered axons, ADH secretion

resumes.

2. If GH is administered to young people before growth of their long

bones is complete,it causes their long bones to grow and they will

grow taller.To accomplish this,however,GH would have to be

administered over a considerable length oftime. It’s likely that some

symptoms ofacromegaly would develop. In addition to undesirable

changes in the skeleton,nerves frequently are compressed as a result

ofthe proliferation of connective tissue. Because GH spares glucose

usage,chronic hyperglycemia results, frequently leading to diabetes

mellitus and the development ofsevere atherosclerosis. Mr. Hoops’s

doctor would therefore not prescribe GH.

3. Surgical removal of the thyroid gland cause T

and T

levels to

decline in the blood.TRH and TSH levels in the blood increase

because,as T

and T

levels in the blood decrease,the negative

feedback effect ofT

and T

on TRH and TSH are removed.Oral

administration ofT

and T

cause blood levels ofT

and T

increase and,because of negative feedback, TRH and TSH levels

decline.

4. In response to a reduced dietary intake ofcalcium, the blood levels

ofcalcium begin to decline. In response to the decline in blood

levels ofcalcium, an increase of PTH secretion from the parathyroid

glands occurs.The PTH functions to increase calcium resorption

from bone.Consequently, blood levels of calcium are maintained

within the normal range but,at the same time, bones are being

decalciﬁed.Severe dietary calcium deﬁciency results in bones that

become soft and eaten away because ofthe decrease in calcium

content.

5. Removal ofthe thyroid gland means that the tissue responsible for

thyroid hormone (T

and T

) secretion from thyroid follicles,and

calcitonin from parafollicular cells,would no longer occur.However,

blood Ca

would remain within its normal range.Calcitonin is not

essential for the maintenance ofnormal blood Ca

levels.Removal

ofthe parathyroid gland would eliminate PTH secretion. Without

PTH,blood levels of calcium fall. When the blood levels of calcium

fall below normal,the permeability of nerve and muscle cells to Na

increases.As a consequence, spontaneous action potentials are

produced that cause tetanus ofmuscles. Death can result from

tetany ofrespiratory muscles.

6. High aldosterone levels in the blood lead to elevated Na



levels in

the circulatory system and low blood levels ofK



.The effect of low

blood levels ofK



is hyperpolarization ofmuscle and neurons. The

hyperpolarization results from the lower levels ofK



in the

extracellular ﬂuid and a greater tendency for K



to diffuse from the

cell.As a result, a greater-than-normal stimulus is required to cause

the cells to depolarize to threshold and generate an action potential.

Symptoms oflow serum K



levels therefore include lethargy and

muscle weakness.Elevated Na



concentrations result in a greater-

than-normal amount ofwater retention in the circulatory system,

which can result in elevated blood pressure.The major effect of a

low rate ofaldosterone secretion is elevated blood K



levels.As a

result,nerve and muscle cells partially depolarize. Because of their

partial depolarization,they produce action potentials spontaneously

or in response to very small stimuli.The result is muscle spasms, or

tetanus.

7. Large doses of cortisone can damage the adrenal cortex because

cortisone inhibits ACTH secretion from the anterior pituitary.

ACTH is required to keep the adrenal cortex from undergoing

atrophy.Prolonged use of large doses of cortisone can cause the

adrenal gland to atrophy to the point at which it cannot recover if

ACTH secretion does increase again.

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

18. Endocrine Glands

Companies, 2004

8. An increase in insulin secretion in response to parasympathetic

stimulation and gastrointestinal hormones is consistent with the

maintenance ofhomeostasis because parasympathetic stimulation

and increased gastrointestinal hormones result from conditions

such as eating a meal.Insulin levels therefore increase just before

large amounts ofglucose and amino acids enter the circulatory

system.The elevated insulin levels prevent a large increase in blood

glucose and the loss ofglucose in the urine.

9. In response to a meal high in carbohydrates,insulin secretion is

increased,and glucagon secretion is reduced. The stimulus for the

insulin secretion comes from parasympathetic stimulation and,more

importantly,from elevated blood levels of glucose. Target tissues take

up glucose and blood glucose levels remain within a normal range.

In response to a meal high in protein but low in carbohydrates,

insulin secretion is increased slightly,and glucagon secretion is also

increased.The lower insulin secretion causes some increase. Insulin

secretion is stimulated by the parasympathetic system and an

increase in blood amino acid levels.Glucagon is stimulated by low

blood glucose levels and by some amino acids.In the rate of glucose

uptake and amino acid uptake,but the rate of uptake is not great

enough to cause blood glucose levels to fall below normal values.

Glucagon also causes glucose to be released from the liver.During

periods ofexercise, sympathetic stimulation inhibits insulin

secretion.As blood glucose levels decline, an increase of glucagon

secretion occurs.The lower rate of insulin secretion decreases the

rate at which tissues such as skeletal muscle take up glucose.Muscle

depends on intracellular glycogen and fatty acids for energy.Blood

glucose levels are maintained within its normal range ofvalues.

Glucagon prevents glucose levels from decreasing too much.

Part3 Integration and ControlSystems638

10. Sympathetic stimulation during exercise inhibits insulin secretion.

Blood glucose levels are not high because skeletal muscle tissue

continues to take up some glucose and metabolizes it.Muscle

contraction depends on glucose stored in the form ofglycogen in

muscles and fatty acid metabolism.During a long run, glycogen

levels are depleted.The “kick”at the end of the r ace results from

increased energy production through anaerobic respiration,which

uses glucose or glycogen as an energy source.Because blood glucose

levels and glycogen levels are low,the source of energy is insufﬁcient

for greatly increased muscle activity.

11. Increased sugar intake will result in elevated blood glucose levels.

The elevated blood glucose levels can lead to polyuria and to

increased osmolality ofthe body ﬂuids. That results in dehydration

ofneurons. As a result some of the neural symptoms of untreated

diabetes,such as irritability and a general sensation of not feeling

well,occur. Billy may also experience a sudden increase in weight

gain because ofincreased sugar intake and insulin administration.

In addition,he may have an increased chance of infections, such as

urinary tract infections.Many of the long-term consequences of

diabetes,such as nephropathies, neuropathies, atherosclerosis,and

others,develop much more rapidly.

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