Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

17. Functional Organization

of the Endocrine System

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The nervous and endocrine systems

are the two major regulatorysystems

of the body, and together theyregu-

late and coordinate the activityof es-

sentially all other body structures. The

nervous system functions something like

telephone messages sent along telephone

wires to their destination. Ittransmits informa-

tion in the form ofaction potentials along the axons of

nerve cells. Chemicalsignals in the form of neurotransmitters are released at

synapsesbetween neurons and the cells they control. The endocrine system is

more like radio signalsbroadcast widelythat everyone with radios tuned to the

proper channelcan receive. It sends information to the cells it controls in the

form ofchemical signals released from endocrine glands. The chemicalsignals

are carried to allparts of the body by the circulatory system. Cells thatare able

to recognize the chemicalsignals respond to them and other cellsdo not.

Thischapter introduces the general characteristicsof the endocrine sys-

tem. Itcompares some of the functions of the nervous and endocrine systems,

emphasizesthe role of the endocrine system in the maintenance of homeosta-

sis, and illustrates the meansby which the endocrine system regulates the

functions of cells. This chapter explains the general characteristicsof the

endocrine system(572), the chemical structure of hormones (573), the control

of secretion rate(573), transportand distribution in the body (578), metabolism

and excretion(580), interaction of hormoneswith their target tissues (581), and

classes of hormone receptors (583). The structure and function ofthe en-

docrine glands, the chemicalsthey secrete, and the means by which activities

are regulated are described in chapter 18.

Colorized TEM of a growth hormone-secreting

cell from the anteriorpituitary gland. The

secretoryvesicles (brown) contain growth

hormone.

CHAPTER

Functional

Organization

of the

Endocrine

System

Part 3 Integration and ControlSystems

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

17. Functional Organization

of the Endocrine System

Companies, 2004

General Characteristicsof the

Endocrine System

Objectives

■ Deﬁne the termsendocrine gland, endocrine system, and

hormone.

■ Describe the functional relationship between the nervous

system and endocrine system.

■ Deﬁne and give examplesof extracellular orintercellular

chemical signals.

The term endocrine (en⬘do¯-krin) is derived from the Greek

wordsendo, meaning within, and crino, to separate.The term implies

that cells ofendocrine glands secrete chemical signals that inﬂuence

tissues that are separated from the endocrine glands by some dis-

tance. The endocrine system is composed of glands that secrete

chemical signals into the circulatory system (ﬁgure 17.1). In con-

trast, exocrine glands have ducts that carry their secretions to sur-

faces (see chapter 4).The secretory products of endocrine glands are

calledhor mones (ho¯r⬘mo¯nz),a term derived from the Greek word

hormon,meaning to set into motion. Traditionally,a hormone is de-

ﬁned as a chemical signal,or ligand, that (1) is produced in minute

amounts by a collection of cells; (2) is secreted into the interstitial

spaces; (3) enters the circulatory system, where it is transported

some distance;and (4) acts on speciﬁc tissues called target tissues at

another site in the body to inﬂuence the activity ofthose tissues in a

speciﬁc fashion.All hormones exhibit most components of this def-

inition,but some components don’t apply to every hormone.

Both the endocrine system and the nervous system regulate

the activities of structures in the body,but they do so in different

ways.For example, hormones secreted by most endocrine glands

Part3 Integration and ControlSystems572

can be described as amplitude-modulated signals (am⬘pli-tood

mod-u¯-la¯t⬘ed),which consist mainly of increases or decreases in

the concentration of hormones in the body ﬂuids (ﬁgure 17.2a).

The effects produced by the hormones either increase or decrease

responses as a function of the hormone concentration. On the

other hand,the all-or-none action potentials carried along axons

can be described as frequency-modulated signals (ﬁgure 17.2b),

which vary in frequency but not in amplitude.A low frequency of

action potentials is a weak stimulus,whereas a high frequency of

action potentials is a strong stimulus (see chapter 11). The re-

sponses of the endocrine system are usually slower and of longer

duration,and its effects are usually more generally distributed than

those ofthe ner vous system.

Although the stated differences between the endocrine and

nervous systems are generally true,exceptions exist. For example,

some endocrine responses are more rapid than some neural re-

sponses, and some endocrine responses have a shorter duration

than some neural responses. In addition, some hormones act as

both amplitude- and frequency-modulated signals, in which the

concentrations of the hormones and the frequencies at which the

increases in hormone concentrations occur are important.

At one time,the endocr ine system was believed to be rela-

tively independent and different from the nervous system.An inti-

mate relationship between these systems is now recognized,

however,and the two systems cannot be completely separated ei-

ther anatomically or functionally.Some neurons secrete chemical

signals called neurohormones (noor-o¯-ho¯r⬘mo¯nz) into the circu-

latory system,which function like hormones. Also, some neurons

directly innervate endocrine glands and inﬂuence their secretory

Spinal cord

Hypothalamus

Pituitary

Thymus

Adrenals

Ovaries

(female)

Pineal

body

Thyroid

Parathyroids

(posterior

part of

thyroid)

Pancreas

(islets)

Testes

(male)

Figure 17.1

Endocrine Glands

The location ofmajor endocrine glands in the human body.

Time

Weak

signal

Strong

signal

Stronger

signal

Hormone concentration

in blood

Time

(mV)

–85

Weak

signal

Strong

signal

Stronger

signal

Figure 17.2

RegulatorySystems

(a)Amplitude-modulated system. The concentration ofthe hormone

determinesthe strength of the signal and the magnitude of the response.

Formost hormones, a small concentration of a hormone isa weak signal and

producesa small response, whereas a larger concentration isa stronger signal

and resultsin a greater response. (b) Frequency-modulated system.The

strength ofthe signal depends on the frequency, not the size, of the action

potentials. Allaction potentials are the same size in a given tissue. A low

frequencyof action potentials is a weak stimulus, and a higher frequency is

astronger stimulus.

(a) (b)

Seeley−Stephens−Tate:

Anatomy and Physiology,

Sixth Edition

III. Integration and Control

Systems

17. Functional Organization

of the Endocrine System

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Chapter 17 FunctionalOrganization of the Endocrine System 573

activity.Neurons release chemical signals at synapses in the form of

neurotransmitters and neuromodulators,and the membrane po-

tentials of some endocrine glands undergo depolarization or hy-

perpolarization,which results in either an increase or a decrease in

the rate of hormone secretion. Conversely,some hormones se-

creted by endocrine glands affect the nervous system and markedly

inﬂuence its activity.

Intercellular chemical signalsallow one cell to communi-

cate with other cells.These signals coordinate and regulate the ac-

tivities of most cells.Neurotransmitters and neuromodulators are

intercellular chemical signals that play important roles in the func-

tion of the nervous system (see chapter 11).Hormones are inter-

cellular chemical signals secreted by endocrine glands.

Autocrine (aw⬘to¯-krin) chemical signalsare released by

cells and have a local effect on the same cell type from which

thechemical signals are released. Examples include prostaglandin-

like chemicals released from smooth muscle cells and platelets in

response to inﬂammation.These chemicals cause the relaxation of

blood vessel smooth muscle cells and the aggregation ofplatelets.

As a result,the blood vessels dilate and blood clots.

Paracrine (par⬘a˘-krin) chemical signals are released by

cells and affect other cell types locally without being transported in

the blood.For example, a peptide called somatostatin is released by

cells in the pancreas and functions locally to inhibit the secretion of

insulin from other cells ofthe pancreas (see chapter 18).

Pheromones(fer⬘o¯-mo¯nz) are chemical signals secreted into

the environment that modify the behavior and the physiology of

other individuals.For example, pheromones released in the urine

of cats and dogs at certain times are olfactory signals that indicate

fertility.Evidence supports the existence of pheromones produced

by women that inﬂuence the length of menstrual cycles in other

women (table 17.1).

Many intercellular chemical signals consistently ﬁt one spe-

ciﬁc deﬁnition, but others do not. For example,norepinephrine

functions both as a neurotransmitter and a neurohormone; and

prostaglandins function as neurotransmitters, neuromodulators,

parahormones,and autocrine chemical signals. The schemes used

to classify chemicals on the basis of their functions are useful,but

they don’t indicate that a speciﬁc molecule always performs as the

same type of chemical signal in every place it’s found.For that rea-

son, the study of endocrinology often includes the study of au-

tocrine and paracrine chemical signals in addition to hormones.

1. Deﬁne the terms endocrine gland, endocrine system, and

hormone. Explain whya simple deﬁnition for hormone is

difﬁcultto create.

2. Contrast the endocrine system and the nervous system for

the following: amplitude versusfrequency modulation;

speed and duration of targetcell response.

3. Explain why, despite their differences, the nervous and

endocrine systemscannot be completely separated.

4. Name and describe ﬁve intercellular chemical signals,

otherthan hormones.

Chemical Structure ofHormones

Objective

■ Describe the categoriesof hormones based on their

chemical structure.

Hormones,including neurohormones, can be either proteins,

short sequences of amino acids called polypeptides, derivatives of

amino acids,or lipids. Some protein hormones, called glycoprotein

hormones, are composed of one or more polypeptide chains and

carbohydrate molecules.Lipid hormones are either steroids or de-

rivatives offatty acids. Table 17.2 and ﬁgure 17.3 provide informa-

tion concerning the chemical structure ofthe major hormones.

5. List six categories of hormones based on chemical

structure, and give an example of each.

Controlof Secretion Rate

Objective

■ Explain howregulation of hormone secretion is achieved.

Most hormones are not secreted at a constant rate.Instead,

most endocrine glands increase and decrease their secretory activity

dramatically over time.The speciﬁc mechanisms that regulate the se-

cretion rates for each hormone are presented in chapter 18,but the

general patterns of regulation are introduced in this chapter.Hor-

mones function to regulate the rates ofmany activities in the body.

The secretion rate ofeach hormone is controlled by a negative-feed-

back mechanism (see chapter 1),so that the body activity it regulates

is maintained within a normal range and homeostasis is maintained.

Hormones have three major patterns ofregulation. One pat-

tern involves the action ofa substance other than a hormone on

the endocrine gland. Figure 17.4 describes the inﬂuence of blood

glucose on insulin secretion from the pancreas. An increasing

blood glucose level causes an increase in insulin secretion from the

pancreas.Insulin increases glucose movement into cells, resulting

in a decrease in blood glucose levels, which in turn causes a de-

crease in insulin secretion. Thus insulin levels increase and de-

crease in response to changes in blood glucose levels.

A second pattern of hormone regulation involves neural

control ofthe endocrine gland. Neurons synapse with the cells that

produce the hormone,and, when action potentials result, the neu-

rons release a neurotransmitter.In some cases,the neurotransmitter

is stimulatory and causes the cells to increase hormone secretion.In

other cases the neurotransmitter is inhibitory and decreases

hormone secretion. Thus sensory input and emotions acting

through the nervous system can inﬂuence hormone secretion.Fig-

ure 17.5 illustrates the neural control of epinephrine and norepi-

nephrine secretion from the adrenal gland.In response to stimuli

such as stress or exercise,the nervous system stimulates the adrenal

gland to secrete epinephrine and norepinephrine, which help the

body respond to the stimuli.When the stimuli are no longer pres-

ent,secretion of epinephrine and norepinephrine decreases.

Seeley−Stephens−Tate:

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Table 17.1

Intercellular

Chemical

Signal Description Example

Functional Classification of Intercellular Chemical Signals

Paracrine

chemical

signal

ineAutocr

chemical

signal

Hormone

mone

Neuron

Neurohor

Pheromone

Autocrine Secreted by cells in a local Prostaglandins

area and influences the

activity of the same cell

type from which it was

secreted

Paracrine Produced by a wide variety of Histamine

tissues and secreted into prostaglandins

tissue spaces; usually has

a localized effect on other

tissues

Hormone Secreted into the blood by Thyroxine, insulin

specialized cells; travels

some distance to target

tissues; influences specific

activities

Neurohormone Produced by neuronsand Oxytocin, antidiuretic

functions like hormones hormone

Neurotransmitter Produced by neurons and Acetylcholine,

or neuromodulator secreted into extracellular epinephrine

spaces by presynaptic

nerve terminals; travels

short distances; influences

postsynaptic cells

Pheromone Secreted into the Sexpheromones are released

environment; modifies by humans and many other

physiology and behavior of animals. They are released in

other individuals the urine of animals, such as

dogs and cats. Pheromones

produced by women influence

the length of the menstrual

cycle of other women.

Neuron

Neurotransmitter

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Table 17.2

Structural

Category Examples

Structural

Category Examples

Proteins Growth hormone

Prolactin

Insulin

Glycoproteins (protein and Follicle-stimulating hormone

carbohydrate) Luteinizing hormone

Thyroid-stimulating hormone

Parathyroid hormone

Polypeptides Thyrotropin-releasing hormone

Oxytocin

Antidiuretic hormone

Calcitonin

Glucagon

Adrenocorticotropic hormone

Endorphins

Thymosin

Melanocyte-stimulating hormones

Hypothalamic hormones

Lipotropins

Somatostatin

Structural Categories of Hormones

Amino acid derivatives Epinephrine

Norepinephrine

Thyroid hormones (both T

and T

)

Melatonin

Lipids

Steroids (cholesterol is a Estrogens

precursor for all steroids) Progestins (progesterone)

Testosterone

Mineralocorticoids (aldosterone)

Glucocorticoids (cortisol)

Fatty acids Prostaglandins

Thromboxanes

Prostacyclins

Leukotrienes

Abbreviations:T

⫽ tetraiodothyronine or thyroxine; T

⫽ triiodothyronine.

Proteins

Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Try-Gln-Leu-Glu-Asn-Tyr Cys-Asn

A chain

B chain

Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Try-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr

Peptides

Cys-Try-Ile-Gln-Asn-Cys-Pro-Leu-Gly

Oxytocin

Amino acid derivatives

OHO

HNH

C COOH

Triiodothyronine (T

)

OHO

HNH

C COOH

Tetraiodothyronine or thyroxine (T

)

Lipids and steroids

Steroids

Testosterone

Prostaglandin F

2␣

(PGF

2␣

)

COOH

Formed from

fatty acids

Insulin

Figure 17.3

The

ChemicalStructure of

Hormones

(a) Insulin isan example of

a protein hormone.

(b) Oxytocin isan example

ofa peptide hormone.

triiodothyronine (T

)

and tetraiodothyronine (T

are examplesof modiﬁed

amino acid hormones.

(d) Testosterone, a steroid,

and prostaglandin F

2␣

are examplesof lipid

hormones.

(a)

(b)

(c)

(d)

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1. Increased blood glucose

stimulates increased insulin

secretion from the pancreas.

2. Insulin increases glucose

uptake by tissues, which

decreases blood glucose

levels.

Adipose

tissue

Skeletal muscle

tissue

Insulin

Pancreas

Blood glucose

ProcessFigure 17.4

NonhormonalRegulation of Hormone Secretion

Glucose, which isnot a hormone, regulates the secretion of insulin from the pancreas.

Stress or

exercise

Epinephrine

and norepinephrine

Adrenal

medulla

Sympathetic

chain

Preganglionic

sympathetic

neurons

1. Stimuli such as stress or exercise

activate the sympathetic division of

the autonomic nervous system.

2. Sympathetic neurons stimulate the

release of epinephrine and smaller

amounts of norepinephrine from the

adrenal medulla. Epinephrine and

norepinephrine prepare the body to

respond to stressful conditions.

Once the stressful stimuli are

removed, less epinephrine is released

as a result of decreased stimulation

from the autonomic nervous system.

ProcessFigure 17.5

NervousSystem Regulation of Hormone Secretion

The sympatheticdivision of the autonomic nervous system stimulates the adrenal gland to secrete epinephrine and norepinephrine.

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Chapter 17 FunctionalOrganization of the Endocrine System 577

A third pattern of hormone regulation involves the control

ofthe secretory activit y of one endocrine gland by a hormone or a

neurohormone secreted by another endocrine gland. Figure 17.6

illustrates how thyroid-releasing hormone (TRH) from the hypo-

thalamus ofthe brain stimulates the secretion of thyroid-stimulating

hormone (TSH) from the anterior pituitary gland,which, in turn,

stimulates the secretion of thyroid hormones from the thyroid

gland.A negative-feedback mechanism for regulating thyroid hor-

mone secretion exists because thyroid hormones can inhibit the se-

cretion ofTRH and TSH. Thus, the concentrations of TRH, TSH,

and thyroid hormone increase and decrease within a normal range

(see chapter 18).

NeuralControl of Insulin Secretion

Blood glucose levelsregulate insulin secretion, but insulin secretion is

also regulated bythe nervous system. When action potentials in

parasympatheticneurons that innervate the pancreas increase, the

neurotransmitter acetylcholine isreleased. Acetylcholine causes

depolarization ofpancreatic cells, and insulin is secreted. When action

potentialsin sympathetic neurons that innervate the pancreas increase,

the neurotransmitter norepinephrine isreleased. Norepinephrine causes

hyperpolarization ofpancreatic cells, and insulin secretion decreases.

Thus, nervousstimulation of the pancreas can either increase or

decrease insulin secretion.

PREDICT

For a person having normalthyroid function, the rate at which TSH and

thyroid hormonesare secreted remains within a normal range of

concentrations. In some people, however, the immune system begins

to produce large amountsof an abnormal substance thatfunctions

like TSH. Predictwhat that substance willdo to the rate of TSH

secretion and the rate ofthyroid hormone secretion.

One of these three major patterns by which hormone secre-

tion is regulated applies to each hormone,but the complete picture

isn’t quite so simple.The regulation of hormone secretion often in-

volves more than one mechanism.For example, both the concen-

tration of blood glucose and the autonomic nervous system

inﬂuence insulin secretion from the pancreas.

A few examples of positive-feedback regulation in the en-

docrine system exist. Prior to ovulation,estrogen from the ovary

stimulates luteinizing hormone (LH) secretion from the anterior

pituitary gland.LH, in turn, stimulates estrogen secretion from the

ovary.Consequently,blood levels of estrogen and LH increase prior

to ovulation (ﬁgure 17.7a).The release of oxytocin during delivery

ofan infant is another example (see chapters 28 and 29). In cases of

positive feedback,negative feedback limits the degree to which pos-

itive feedback proceeds (ﬁgure 17.7b).For example, after ovulation

the ovary secretes progesterone,which inhibits LH secretion.

Some hormones are in the circulatory system at relatively con-

stant levels,some change suddenly in response to certain stimuli, and

others change in relatively constant cycles (ﬁgure 17.8).For example,

thyroid hormones in the blood vary within a small range of concen-

trations that remain relatively constant.Epinephrine is released in

large amounts in response to stress or physical exercise;thus its con-

centration can change suddenly.Reproductive hormones increase and

decrease in a cyclic fashion in women during their reproductive years.

6. Describe and give examples of the three major patterns by

which hormone secretion isregulated. Give an example of a

hormone thatis controlled by more than one mechanism.

7. Is hormone secretion generally regulated by negative-

feedbackor positive-feedback mechanisms?

8. Describe chronic, acute, and cyclic patterns of hormone

secretion.

Stimulatory

Inhibitory

TRH

Hypothalamus

Target tissues

TSH

pituitary

Thyroid gland

andT

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

the hypothalamus and travels in the blood to the anterior

pituitary gland.

2. TRH stimulates the release of thyroid-stimulating hormone

(TSH) from the anterior pituitary gland. TSH travels in the

blood to the thyroid gland.

3. TSH stimulates the secretion of thyroid hormones (T

and T

)

from the thyroid gland into the blood.

4. Thyroid hormones act on tissues to produce responses.

5. Thyroid hormones also have a negative-feedback effect on the

hypothalamus and the anterior pituitary to inhibit both TRH

secretion and TSH secretion. The negative feedback helps

keep blood thyroid hormone levels within a narrow range.

Negative feedback

ProcessFigure 17.6

HormonalRegulation of Hormone Secretion

Hormonescan stimulate or inhibit the secretion of other hormones.

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tration of the free hormone molecules decreases in the blood,

fewer hormone molecules diffuse from the capillaries into the in-

terstitial spaces and bind to target cells (ﬁgure 17.9).

Hormones that bind to plasma proteins do so in a reversible

fashion. An equilibrium is established between the free plasma

hormones and hormones bound to plasma proteins called binding

proteins.

H ⫹ BP ←→ HBP

Hormone Binding Hormone bound

protein to binding protein

Many hormones bind only to certain types ofplasma proteins.

For example, a speciﬁc type of plasma protein binds to thyroid

Transport and Distribution

in the Body

Objective

■ Describe howhormones are transported in the blood and

delivered to cells.

Hormones are dissolved in blood plasma and transported ei-

ther in a free form or bound to plasma proteins.Hormones that are

free in the plasma can diffuse from capillaries into interstitial

spaces.As the concentration of free hormone molecules increases

in the blood,more hormone molecules diffuse from the capillaries

into the interstitial spaces and bind to target cells.As the concen-

Ovary

pituitary

Before ovulation

(LH)

Estrogen

Positive

feedback

GnRH

1. During the menstrual cycle, before ovulation, small

amounts of estrogen are secreted from the ovary.

2. Estrogen stimulates the release of gonadotropin-releasing

hormone (GnRH) from the hypothalamus and luteinizing

hormone (LH) from the anterior pituitary.

3. GnRH also stimulates the release of LH from the anterior

pituitary.

4. LH causes the release of additional estrogen from the

ovary. The GnRH and LH levels in the blood increase

because of this positive-feedback effect.

1. During the menstrual cycle, after ovulation, the ovary

begins to secrete progesterone in response to LH.

2. Progesterone inhibits the release of GnRH from the

hypothalamus and LH from the anterior pituitary.

3. Decreased GnRH release from the hypothalamus reduces

LH secretion from the anterior pituitary. GnRH and LH

levels in the blood decrease because of this negative-

feedback effect.

Ovary

pituitary

After ovulation

Negative

feedback

GnRH

Progesterone

Stimulatory

Inhibitory

ProcessFigure 17.7

Positive and Negative Feedback

(a)

(b)

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Chapter 17 FunctionalOrganization of the Endocrine System 579

from the blood because free hormones are rapidly eliminated from

the circulation through either the kidney or the liver (ﬁgure 17.10).

Because hormones circulate in the blood, they are distrib-

uted quickly throughout the body.They diffuse through the capil-

lary endothelium and enter the interstitial spaces,although the rate

at which this movement occurs varies from one hormone to the

next.Lipid-soluble hormones readily diffuse through the walls of

hormones,and a different type of plasma protein binds to sex hor-

mones,such as testosterone. The equilibrium between the unbound

hormone and the hormone bound to the plasma proteins is impor-

tant because only the free hormone is able to diffuse through capil-

lary walls and bind to target tissues. Hormones bound to plasma

proteins tend to remain at a relatively constant level in the blood for

longer periods of time (see next section). A large decrease in the

plasma protein concentration can result in the loss of a hormone

Time

Hormone levels in blood

Time (minutes or hours)

Hormone levels in blood

Time (days)

Hormone levels in blood

Stimulus Stimulus

Figure 17.8

Changesin Hormone Secretion Through Time

Atleast three basic patterns of hormone secretion exist. (a) Chronichormone

regulation—the maintenance ofa relatively constantconcentration of

hormone in the circulating blood over a relativelylong period. (b) Acute

hormone regulation—a hormone rapidlyincreases in the blood for a short

time in response to a stimulus. (c)Cyclic hormone regulation—a hormone is

regulated so thatit increases and decreases in the blood at a relatively

constanttime and to roughly the same amount.

Capillary

High concentration

of hormone

Target cells

Circulating

blood

Circulating

blood

Capillary

Low concentration

of hormone

Target cells

Figure 17.9

Hormone Concentrationsat the TargetCell

Hormone moleculesdiffuse from the blood through the walls of the capillaries

into the interstitialspaces. Once within the interstitial spaces, they diffuse to

the targetcells. (a) As the concentration offree hormone molecules increases

in the blood, more moleculesdiffuse from the capillary to the target cells.

(b)As the concentration of free hormone molecules decreases in the blood,

fewer diffuse from the capillaryto the target cells.

(a)

(b)

(a)

(b)

(c)

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all capillaries. In contrast, water-soluble hormones,such as pro-

teins,must pass through pores called fenestrae (see chapter 21) in

the capillary endothelium.The capillar y endothelia of organs that

are regulated by protein hormones have large pores.

Part3 Integration and ControlSystems

580

9. What effect does a hormone binding to a plasma protein

have on the amountof free hormone in the blood? On the

amountof time the hormone remains in the blood?

10. Why do the capillary endothelia of organs regulated by

protein hormoneshave large pores?

Metabolism and Excretion

Objective

■ Deﬁne half-life, and describe the majorfactors that

increase and decrease the half-life of hormones.

The destruction and elimination of hormones limit the

length oftime during which they are active, and body activities can

increase and decrease quickly when hormones are secreted and re-

main active for only short periods.The length of time it takes for

halfa dose of a substance to be eliminated from the circulatory sys-

tem is called its half-life.The half-life of a hormone is a standard

measurement used by endocrinologists because it allows them to

predict the rate at which hormones are eliminated from the body.

The length of time required for total removal of a hormone from

the body is not as useful because that measurement is inﬂuenced

dramatically by the starting concentration. Water-soluble hor-

mones, such as proteins,glycoproteins, epinephrine, and norepi-

nephrine,have relatively short half-lives because they are degraded

rapidly by enzymes within the circulatory system or organs,such as

the kidneys, liver,or lungs. Hormones with short half-lives nor-

mally have concentrations that increase and decrease rapidly

within the blood. They generally regulate activities that have a

rapid onset and a short duration.

Hormones that are lipid-soluble,such as steroids and thyroid

hormones,commonly circulate in the blood in combination with

plasma proteins.The rate at which hormones are eliminated from

the circulation is greatly reduced when the hormones bind to

plasma proteins.The combination reduces the rate at which they

diffuse through the wall of blood vessels and increases their half-

life.Hormones with a long half-life have blood levels that are main-

tained at a relatively constant level through time. Table 17.3

outlines the ways hormone half-life is shortened or lengthened.

Hormones are removed from the blood in four major ways:ex-

cretion, metabolism,active transport, and conjugation. The kidney

excretes hormones into the urine,or the liver excretes them into the

bile.Enzymes in the blood or in tissues like the liver,kidne y,lungs, or

other target cells metabolize or chemically modify hormones. The

end products can be excreted in the urine or bile,or they can be taken

up by cells and used in metabolic processes.For example,epinephrine

is modiﬁed enzymatically and then excreted by the kidney.Protein

hormones are broken down to their amino acid building blocks.The

amino acids can then be taken up by cells and used to synthesize new

proteins.Some hormones can be actively transported into cells and

recycled.For example, both epinephrine and norepinephrine can be

actively transported into cells and secreted again.

The liver conjugates some hormones.Conjugation (kon-ju˘-

ga¯ ⬘shu˘n) is accomplished when cells in the liver attach water-

soluble molecules to the hormone. These molecules are usually

sulfate or glucuronic acid.Once they are conjugated, hormones are

excreted by the kidney and liver at a greater rate.

Capillary

High concentration

of plasma proteins

Target cells

Circulating

blood

Hormone

Capillary

Low concentration

of plasma proteins

Target cells

Circulating

blood

Hormone

Figure 17.10

Effectof Changes in Plasma Protein

Concentration on the Concentration

ofFree Hormone

(a) An equilibrium existsbetween free hormone molecules and hormone

moleculesbound to plasma proteins. The free hormone molecules can diffuse

from the capillariesto the interstitial spaces. (b) A decrease in plasma protein

concentration reducesthe number of hormone molecules bound to plasma

proteins. Thisincreases the rate at which free hormone moleculesdiffuse from

the capillaries. More importantly, hormonesthat diffuse from capillariesare

eliminated from the blood bythe kidney and liver. The rapid lossof hormone

from the circulatorysystem reduces the hormone concentration in the body

and fewer hormone moleculesare available to bind to receptors.

(a)

(b)

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Chapter 17 FunctionalOrganization of the Endocrine System 581

site.If the protein or glycoprotein molecule is a receptor,the bind-

ing site called a receptor site.The shape and chemical characteris-

tics ofeach receptor site allow only a speciﬁc type of ligand to bind

to it (ﬁgure 17.11).The tendency for each type of ligand to bind to

a speciﬁc type of receptor site, and not to others, is called

speciﬁcity.Insulin therefore binds to insulin receptors but not to

receptors for growth hormone. However,ligands, such as some

hormones, can bind to a number of different receptors that are

closely related. For example,epinephrine can bind to more than

one type of epinephrine receptor.

Hormones are ligands that are secreted and distributed

throughout the body by the circulatory system,but the presence or

absence of speciﬁc receptor molecules in cells determines which

cells will or will not respond to each hormone (ﬁgure 17.12).For

example,there are receptors for TSH in cells of the thyroid gland,

but there are no such receptors in most other cells of the body.

Consequently,cells of the thyroid gland produce a response when

exposed to TSH,but cells without receptor molecules do not re-

spond to it.

Drugs with structures similar to speciﬁc ligands may com-

pete with those ligands for their receptor sites (see chapter 3).De-

pending on the exact characteristics ofa drug, it may either bind to

a receptor site and activate the receptor or it may bind to a receptor

site and inhibit the action ofthe receptor. For example, drugs exist

that compete with the ligand, epinephrine, for its receptor sites.

Some of these drugs activate epinephrine receptors and others in-

hibit them.

The response to a given concentration ofa ligand is constant

in some cases but variable in others.In some cells the response rap-

idly decreases through time. Fatigue of the target cells after pro-

longed stimulation explains some decreases in responsiveness.

Also,the number of receptors can rapidly decrease after exposure

to certain ligands—a phenomenon called down-regulation

(ﬁgure 17.13a).Two known mechanisms are responsible for down-

regulation. First, the rate at which receptors are synthesized de-

creases in some cells after the cells are exposed to a ligand.Because

most receptor molecules are degraded after a time,a decrease in the

Table 17.3 Factors That Influence the Half-Life

of Hormones

A. Means by which the half-life of hormones is shortened:

1. Excretion

Hormones are excreted by the kidney into the urine or excreted by

the liver into the bile.

2. Metabolism

Hormones are enzymatically degraded in the blood, liver, kidney,

lungs, or target tissues. End products of metabolism are either

excreted in urine or bile or used in other metabolic processes by

cells in the body.

3. Active Transport

Some hormones are actively transported into cells and are used

again as either hormones or neurotransmitter substances.

4. Conjugation

Substances such as sulfate or glucuronic acid groups are attached

to hormones primarily in the liver, normally making them less

active as hormones and increasing the rate at which they are

excreted in the urine or bile.

B. Means by which the half-life of hormones is lengthened:

1. Some hormones are protected from rapid excretion or metabolism

by binding reversibly with plasma proteins.

2. Some hormones are protected by their structure. The carbohydrate

components of the glycoprotein hormones protect them from

proteolytic enzymes in the circulatory system.

11. Deﬁne the half-life of a hormone. What happens to this

half-life when a hormone bindsto a plasma protein? What

kindsof hormones bind to plasma proteins?

12. What kinds of activities do hormones with a short half-life

regulate? With a long half-life?

13. What are the ways by which the half-life of a hormone is

shortened orlengthened?

PREDICT

How isthe half-life of a hormone affected by a decrease in the

concentration ofthe speciﬁc plasma protein to which thathormone

binds?

Interaction of Hormones

with Their TargetTissues

Objectives

■ Describe howchemical signals (ligands) bind only to

speciﬁcreceptor sites.

■ Contrastand give examples of down-regulation and up-

regulation.

Chemical signals, commonly called ligands (lig⬘and,

lı¯⬘gand),are molecules that bind to proteins or glycoproteins and

change their functions. Hormones make up one category of li-

gands; others include substances such as neurotransmitters and

chemical mediators ofinﬂammation. The portion of each protein

or glycoprotein molecule where a ligand binds is called a binding

Ligands

Receptor

site

Ligand bound

to its receptor

site

Receptor

(protein or

glycoprotein)

Figure 17.11

Speciﬁcityof Receptors for Ligands

The shape and chemicalcharacteristicsof receptor sites on receptor

moleculesmake them very speciﬁc so that certain ligands can bind to a

receptor site, butothers cannot.

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Part3 Integration and ControlSystems582

creted by the pituitary gland increase the rate ofLH receptor mol-

ecule synthesis in cells of the ovary.Thus, exposure of a tissue to

one hormone can increase its sensitivity to a second by causing up-

regulation in the number ofhormone receptors.

14. Deﬁne chemical signal (ligand) and receptor site. What

characteristicsof the receptor site make itspeciﬁc for one

type of ligand?

15. What is down-regulation? What two mechanisms are

responsible fordown-regulation? Give an example of down-

regulation in the body.

16. What is up-regulation? Give an example of up-regulation in

the body.

Up-regulation

Down-regulation

Target cell GnRH receptor

GnRH

Number of receptors decreases

Time

Target cell

Number of receptors increases

Time

FSH

LH receptor

Figure 17.13

Down-Regulation and Up-Regulation

(a) Down-regulation occurswhen the number of receptors for a hormone

decreaseswithin target cells. For example, gonadotropin-releasing hormone

(GnRH) released from the hypothalamusbinds to GnRH receptors in the

anterior pituitary. GnRH bound to itsreceptors causes down-regulation ofthe

GnRH receptorsso that eventually the target cellsbecome less sensitive to the

GnRH. (b) Up-regulation occurswhen some stimulus causes the number of

receptorsfor a hormone to increase within a target cell. For example, FSH acts

on cellsof the ovary to up-regulate the number of receptors for LH. Thusthe

ovarybecomes more sensitive to the effect of LH.

synthesis rate reduces the total number ofreceptor molecules in a

cell.Second, the combination of ligands and receptors can increase

the rate at which receptor molecules are degraded.In some cases,

when a ligand binds to a receptor,both the ligand and the receptor

are taken into the cell by phagocytosis.Once the hormone and re-

ceptor are inside the cell,the cell can break them down.

Gonadotropin-releasing hormone (GnRH),which is released

from neurons ofthe hypothalamus, causes the secretion of LH and

follicle-stimulating hormone (FSH) from the anterior pituitary cells.

In addition,exposure of the anterior pituitary cells to GnRH causes

the number of receptor molecules for GnRH in the pituitary gland

cells to dramatically decrease several hours after exposure to the hor-

mone.The down-regulation of GnRH receptors causes the pituitary

gland to become less sensitive to additional GnRH.The normal re-

sponse of the pituitary gland cells to GnRH, therefore,depends on

periodic rather than constant exposure ofthe gland to the hormone.

In general, tissues that exhibit down-regulation of receptor

molecules are adapted to respond to short-term increases in hor-

mone concentrations,and tissues that respond to hormones main-

tained at constant levels normally do not exhibit down-regulation.

In addition to down-regulation, periodic increases in the

sensitivity of some cells to certain hormones also occur. This is

calledup-regulation, and it results from an increase in the rate of

receptor molecule synthesis (ﬁgure 17.13b).An example of up-

regulation is the increased number ofreceptor molecules for LH in

cells of the ovary during each menstrual cycle. FSH molecules se-

(a)

(b)

Capillary

Target cells

for TSH

TSH receptor

Receptor

Circulating

blood

TSH

Nontarget

cells

Figure 17.12

Response ofTarget Cellsto Hormones

TSH issecreted into the blood and distributed throughout the body, where

TSH diffusesfrom the blood into the interstitial ﬂuid. Only target cells,

however, have receptorsfor TSH; therefore, although TSH isdistributed

throughoutthe body, only target cellsfor that hormone can respond to it.

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Chapter 17 FunctionalOrganization of the Endocrine System 583

PREDICT

Estrogen isa hormone secreted by the ovary. It issecreted in greater

amountsafter menstruation and a few days before ovulation. Among

itsmany effects is causing up-regulation of receptorsin the uterus for

another hormone secreted bythe ovary called progesterone.

Progesterone issecreted after ovulation. A major effect of

progesterone isto cause the uterus to become ready for the embryo to

attach to itswall following ovulation. Pregnancycannot occur unless

the embryo attachesto the wall of the uterus. Predict the

consequence ifthe ovary secretes too little estrogen.

Classes ofHormone Receptors

Objective

■ Listthe two major categories into which ligands are placed.

Hormones,like other ligands, can be placed into two major

categories.

1. Ligands that cannot pass through the plasma membrane.

These ligands include large molecules and water-soluble

molecules that cannot pass through the plasma membrane.

They interact with membrane-bound receptors,which are

receptors that extend across the plasma membrane and have

their receptor sites exposed to the outer surface ofthe

plasma membrane (ﬁgure 17.14a).When a ligand binds to

the receptor site on the outside ofthe plasma membrane,

the receptor initiates a response inside the cell.These

ligands include many large hormones that are proteins,

glycoproteins,polypeptides, and some smaller molecules

such as epinephrine and norepinephrine.

2. Ligands that pass through the plasma membrane.These

ligands are lipid-soluble and relatively small.They diffuse

through the plasma membrane and bind to intracellular

receptors, which are receptors in the cytoplasm or in the

nucleus ofthe cell (ﬁgure 17.14b). Subsequently, the

receptors,with the ligands bound to their receptor sites,

interact with DNA in the nucleus ofthe cell or interact with

existing enzymes to produce a response.Thyroid hormones

and steroid hormones,such as testosterone, estrogen,

progesterone,aldosterone, and cortisol are examples.

17. Deﬁne membrane-bound receptor and intracellular

receptor. Describe the typesof molecules that bind to each

type of receptor.

Membrane-Bound Hormone Receptors

Objectives

■ Describe howligands directly affect membrane

permeability.

■ Explain howligands interact with receptors to inﬂuence G

proteins, and listthe ways G proteins can produce a

response to a ligand.

■ Describe howligands interact with receptors to produce

intracellularmediator molecules.

■ Describe howligands bind with receptors and alter the

activityof intracellular enzymes.

Ligands bind in a reversible fashion to the receptor sites of

membrane-bound receptor molecules. Hormone receptor mole-

cules have peptide chains that cross the membrane once in the case

ofsome receptors and several times for other receptors (see chapter

3).After a hormone binds to its receptor site,the intracellular par t of

the receptor initiates events that lead to a response.The mechanisms

by which all membrane-bound receptors produce an intracellular

response is not known,but evidence exists for at least three major

mechanisms.The results of ligands binding to membrane-bound

receptors are to (1) directly change the permeability ofthe plasma

membrane by opening or closing ion channels,(2) alter the activ-

ity of G proteins at the inner surface of the plasma membrane,

Ligand

Receptor site

Plasma

membrane

Membrane-bound

receptor

Ligand

Receptor site

Plasma

membrane

Intracellular

receptor

Figure 17.14

Membrane-Bound and Intracellular Receptors

(a) A ligand combineswith the receptor site of a membrane-bound receptor. The receptor site isexposed to the outside of the cell, and the receptor extends across

the plasma membrane. (b) The small, lipid-soluble ligand diffusesthrough the plasma membrane and combineswith the receptor site of an intracellular receptor.

(a)

(b)

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(3) or alter the activity of intracellular enzymes (table 17.4). The

changes,initiated by the combination of ligands with their recep-

tor sites,produce speciﬁc responses in cells.

ReceptorsThat Directly Alter Membrane Permeability

Some membrane-bound receptors are protein molecules that

make up part of ion channels in the plasma membrane (see chap-

ter 3).When ligands bind to the receptor sites of this type of recep-

tor,the combination alters the three-dimensional structure of the

proteins ofthe ion channels, causing the channels either to open or

close.These channels are called ligand-gated ion channels. The re-

sult is a change in the permeability ofthe plasma membrane to the

speciﬁc ions passing through the ion channels (ﬁgure 17.15).For

example,serotonin molecules bind to serotonin receptor sites that

are part of a ligand-gated Na

⫹

channels and cause them to open.

⫹

diffuse into the cell and cause depolarization of the plasma

membrane. Depolarization of target cells may lead to action po-

tential initiation in those cells. Similarly,the neurotransmitter

acetylcholine,released from nerve cells, is a ligand that combines

with membrane-bound receptors of skeletal muscle cells. The

combination of acetylcholine molecules with the receptor sites of

the membrane-bound receptors for acetylcholine opens Na

⫹

channels in the plasma membrane.Consequently, Na

⫹

diffuse into

the skeletal muscle cells causing depolarization and action poten-

tial initiation,and contraction (see chapter 9). Table 17.5 lists ex-

amples of ligand-gated ion channels. Many of these channels

respond to neurotransmitters and not hormones, but some play

important roles in regulating hormone secretion or mediating re-

sponses to paracrine chemical signals.

Part3 Integration and ControlSystems584

ReceptorsThat Activate G Proteins

Many membrane-bound receptors produce responses through the

action of a complex of proteins of the plasma membrane called

Gproteins (table 17.6 and ﬁgure 17.16). G proteins consist of three

subunits; from the largest to smallest, they are called alpha (␣),

beta (␤), and gamma (␥).The G proteins are so named because

one of the subunits binds to guanine nucleotides. In the inactive

state, a guanine diphosphate (GDP) molecule is bound to the ␣

subunit ofeach G protein.

Table 17.4

Hormone

Membrane-bound receptor Intracellular receptor

Receptor linked Receptor linked Receptors linked Activates

to ion channels to G proteins to intracellular genes

enzymes

Opens or closes Activates existing Synthesizes

ion channels enzymes new proteins

or enzymes

Cell response

Overview of Responses of Cellsto Hormones Binding to Their Receptors

channel

(open)

Serotonin bound

to serotonin receptor

site

Figure 17.15

Membrane-Bound ReceptorsThat Directly

ControlMembrane Channels

Membrane-bound receptorsfor serotonin are part of the Na

⫹

channel. When a

serotonin molecule bindsto its receptor site on the serotonin receptor, the

⫹

channelopens and the permeability of the membrane to Na

⫹

increases.

⫹

then diffusesthrough the channels into the cell.

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G proteins can bind with receptors at the inner surface ofthe

plasma membrane.After a ligand binds to the receptor on the out-

side of a cell,the receptor changes shape. As a result, the receptor

combines with a G protein complex on the inner surface of the

plasma membrane,and GDP is released from the ␣ subunit.Gua-

nine triphosphate (GTP), which is more abundant than GDP,

binds to the ␣subunit, thereby activating it. The G proteins sepa-

rate from the receptor and the activated ␣subunit separates from

the ␤ and␥ subunits (see ﬁgure 17.16 1 and 2). The activated ␣

subunit can alter the activity ofmolecules within the plasma mem-

brane or inside the cell,thus producing cellular responses. After a

short time, the activated ␣ subunit is turned off because GTP is

converted to GDP.The ␣ subunit then recombines with the ␤and

␥subunits (see ﬁgure 17.16 3 and 4).

Some activated ␣subunits of G proteins can combine with

ion channels,causing them to open or close (ﬁgure 17.17). For ex-

ample, activated ␣ subunits can open Ca

2⫹

channels in smooth

muscle cells resulting in the movement of Ca

2⫹

into those cells.

The Ca

2⫹

function as intracellular mediators. The ions combine

with calmodulin (kal-mod⬘u¯-lin) molecules, and the calcium-

calmodulin complexes activate enzymes that cause contraction of

the smooth muscle cells (ﬁgure 17.17 1and 2). After a short time,

the activated ␣subunit is inactivated because GTP is converted to

GDP.The ␣ subunit then recombines with the ␤ and ␥subunits

(see 17.17 3and 4).

Other activated ␣subunits of G proteins alter the activity of

enzymes inside of the cell. For example,activated ␣ subunits can

inﬂuence the rate ofcyclic adenosine monophosphate (cAMP) for-

mation (ﬁgure 17.18).The enzy me,adenylate cyclase (a-den⬘i-la¯t

sı¯⬘kla¯s), can be activated by G proteins, thereby increasing the for-

mation ofcAMP from ATP.The cAMP molecules act as intracellu-

lar mediator molecules. They combine with enzymes and alter

their activities inside of the cells, which, in turn, produce re-

sponses. The amount of time cAMP is present to produce a re-

sponse in a cell is limited. An enzyme in the cytoplasm, called

phosphodiesterase (fos⬘fo¯-dı¯-es⬘ter-a¯s), breaks down cAMP to

AMP.The response of the cell is terminated after cAMP levels are

reduced below a certain level.

Cyclic AMP acts as an intracellular mediator in many cell

types. The response in each cell type is different because the en-

zymes activated by cAMP in each cell type are different.For exam-

ple,glucagon combines with receptors on the surface of liver cells,

Table 17.5

Ligand Channel Type Response

Chemical Signals, Including Paracrine, That Bind to Receptors and Directly Control

Ion Channels

Abbreviations:GABA ⫽ gamma(γ)-aminobutyric acid.

Acetylcholine Cation channel (primarily Na

⫹

channels) Excitatory

Serotonin Cation channel (primarily Na

⫹

channels) Excitatory

Glutamate Cation channel (primarily Na

⫹

channels) Excitatory

Glycine Cl

⫺

channels Inhibitory

GABA Cl

⫺

channels Inhibitory

Table 17.6

Hormone Source Target Tissue

Examples of Hormones That Bind to Membrane-Bound Receptors and Activate G Proteins

Luteinizing hormone Anterior pituitary Ovary or testis

Follicle-stimulating hormone Anterior pituitary Ovary or testis

Prolactin Anterior pituitary Ovary or testis

Thyroid-stimulating hormone Anterior pituitary Thyroid gland

Adrenocorticotropic hormone Anterior pituitary Adrenal cortex

Oxytocin Posterior pituitary Uterus

Vasopressin Posterior pituitary Kidney

Calcitonin Thyroid gland (parafollicular cells) Osteoclasts and osteocytes

Parathyroid hormone Parathyroid gland Osteoclasts

Glucagon Pancreas Liver

Epinephrine Medulla of adrenal gland Cardiac muscle

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Ligand

Receptor

site

G protein with

GDP bound to

theα subunit

Membrane-bound

receptor

1. The membrane-bound receptor has a receptor site exposed to the

outside of the cell. The portion of the receptor inside of the cell can

bind to the G protein.

Ligand bound

to receptor site

GTP

GDP

GTP replaces

GDP on α subunit;

α subunit separates

from other subunits

G protein

separates

from receptor

2. The ligand binds to the receptor site of the membrane-bound

receptor. The combination alters the G protein. GTP replaces GDP

on the α subunit, and the α subunit separates from the γ and β subunits.

Theα subunit can influence ion channels in the plasma membrane or

the synthesis of intracellular mediators.

GDP

Phosphorylase

removes

phosphate (P

)

from GTP on

α subunit

3. When the ligand separates from the receptor site, additional G proteins

are no longer activated. Inactivation of the α subunit occurs when

phosphorylase removes an inorganic phosphate (P

) from the GTP,

leaving GDP bound to the α subunit.

GDP

G protein subunits recombine

4. The subunits of the G protein recombine.

Ligand separates

from receptor site

Receptor site

Ligand

Receptor site

GDP

ProcessFigure 17.16

Membrane-Bound ReceptorsThat Activate G Proteins

activating G proteins and causing an increase in cAMP synthesis,

which increases the release of glucose from liver cells (see ﬁgure

17.18).In contrast, LH combines with receptors on the surface of

cells ofthe ovary, activating G proteins, and increasing cAMP syn-

thesis.The major response to the increased cAMP is ovulation.

The combination of ligands with their receptors doesn’t al-

ways result in increased cAMP synthesis.There are other common

intracellular mediators (table 17.7).In some cell types, the combi-

nation of ligands with their receptors causes the G proteins to in-

hibit the synthesis ofcAMP, producing a response.

G proteins can also alter the concentration of intracellular

mediators other than Ca

2⫹

or cAMP (see table 17.7).For example,

Part3 Integration and ControlSystems586

diacylglycerol(dı¯⬘as-il-glis⬘er-ol) (DAG)and inositol (in-o¯⬘si-to¯l,

in-o¯⬘si-tol) triphosphate (IP

) are intracellular mediator mole-

cules that are inﬂuenced by G proteins (ﬁgure 17.19).Epinephrine

binds to certain membrane-bound receptors in some types of

smooth muscle.The combination activates a G protein mechanism,

which,in turn, increases the activity of phospholipase C. Phospho-

lipase C converts phosphoinositol diphosphate (PIP

) to DAG and

. DAG activates enzymes that synthesize prostaglandins.

Prostaglandins increase smooth muscle contraction. IP

releases

2⫹

from the endoplasmic reticulum or opens Ca

2⫹

channels in

the plasma membrane.The ions enter the cy toplasm and increase

contraction ofthe smooth muscle cells.

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Chapter 17 FunctionalOrganization of the Endocrine System 587

ReceptorsThat Alter the Activity of

IntracellularEnzymes

Some ligands bind to membrane-bound receptors and directly

change the activity of an intracellular enzyme. The altered en-

zyme activity either increases or decreases the synthesis of intra-

cellular mediator molecules,or it results in the phosphorylation

of intracellular proteins. The intracellular mediators or phos-

phorylated proteins activate processes that produce the response

ofcells to the ligands.

Intracellular enzymes that are controlled by membrane-

bound receptors can be part ofthe membrane-bound receptor, or

they may be separate molecules.The intracellular mediator mole-

cules act as chemical signals that move from the enzymes that pro-

duce them into the cytoplasm of the cell, where they activate

processes that produce the response ofthe cell.

Cyclic guanine(gwahn⬘e¯n)monophosphate (cGMP) is an

intracellular mediator molecule that is synthesized in response to a

ligand binding with a membrane-bound receptor (ﬁgure 17.20).

The ligand binds to its receptor,and the combination activates an

Ligand bound

to receptor site

Calmodulin

(inactive)

channel

(closed)

GTP replaces

GDP on α subunit

G protein

separates

from receptor

GDP

GTP

1. A ligand binds to the receptor site of the membrane-bound receptor.

The combination alters the G protein. GTP replaces GDP on the

α subunit, and the α subunit separates from the γ and β subunits.

α subunit with GTP

binds to Ca

channel

and causes it to open

GTP

Calmodulin

(active)

bound

to calmodulin

channel

(open)

2. The α subunit, with GTP bound to it, combines with the Ca

channel,

and the combination causes the Ca

channel to open. The ions

diffuse into the cell and combine with calmodulin. The combination of

with calmodulin produces the response of the cell to the

ligand.

Ligand separates

from receptor site

GDP

Phosphorylase

removes phosphate

from GTP on

α subunit

3. Phosphorylase removes an inorganic phosphate from the GTP bound to

theα subunit, leaving GDP bound to the α subunit. The α subunit can

no longer stimulate a cellular response, it separates from the Ca

channel, and the channel closes.

channel

(closed)

Ligand

Receptor site

G protein with

GDP bound to

theα subunit

GDP

channel

(closed)

4. The α subunit recombines with γ and β subunits.

ProcessFigure 17.17

Membrane-Bound Receptors, G Proteins, and Ca

2ⴙ

Channels

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enzyme called guanylyl cyclase (gwahn⬘i-lil sı¯⬘kla¯s) located at the

inner surface of the plasma membrane. The guanylyl cyclase en-

zyme converts guanine triphosphate (GTP) to cGMP and two inor-

ganic phosphate groups.The cGMP molecules then combine with

speciﬁc enzymes in the cytoplasm ofthe cell and activate them. The

activated enzymes,in turn, produce the response of the cell to the

ligand. For example, atrial natriuretic hormone is a ligand that

combines with its receptor in the plasma membrane ofkidney cells.

Part3 Integration and ControlSystems588

The result is an increase in the rate of cGMP synthesis at the inner

surface ofthe plasma membranes (see ﬁgure 17.20). Cyclic GMP in-

ﬂuences the action ofenzymes in the kidney cells, which increase the

rate ofNa

⫹

and water excretion by the kidney (see chapter 26).The

amount oftime the cGMP is present to produce a response in the cell

is limited.Phosphodiesterase breaks down cGMP to GMP. Conse-

quently,the length of time a ligand increases cGMP synthesis and

has an effect on a cell is briefafter the ligand is no longer present.

Glucagon bound to

glucagon receptor

α subunit of G protein

bound to GTP

Adenylate cyclase

catalyzes the

formation of

cAMP

Phosphodiesterase

inactivates cAMP

GDP

ATP

cAMP

AMP

(inactive)

GTP

Protein

kinase

Response

Phosphorylates specific enzymes,

and activates them to break down

glycogen and release glucose

cAMP is an

intracellular mediator

that activates protein

kinases

Figure 17.18

Membrane-Bound ReceptorsThat Activate G Proteins and Increase the Synthesisof cAMP

Membrane-bound receptorsfor glucagon are associated with G proteinsin liver cells. When glucagon binds to glucagon receptors, the ␣ subunitof the G proteins

dissociatesfrom the other subunits and GTP binds to it. The ␣ subunitthen binds to adenylate cyclase and activates it. The resulting increase in cAMP activates

protein kinase enzymes, which phosphorylate other speciﬁcenzymes that breakdown glycogen and release glucose from the liver cells.

Table 17.7

Intracellular Mediator Example of Cell Type Example of Response

Common Intracellular Mediators

Cyclic guanine monophosphate Kidney cells Increases Na

⫹

and water excretion by the kidney

(cGMP)

Cyclic adenosine monophosphate Liver cells Increases the breakdown of glycogen and the release of

(cAMP) glucose into the circulatory system

Calcium ions (Ca

2⫹

) Smooth muscle cells Contraction of smooth muscle cells

Inositol triphosphate (IP

) Smooth muscle cells Contraction of certain smooth muscle cells in response to

epinephrine

Diacylglycerol (DAG) Smooth muscle cells Contraction of certain smooth muscle cells in response to

epinephrine

Nitric oxide (NO) Smooth muscle cells Relaxation of smooth muscle cells of blood vessels resulting

in vasodilation

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Chapter 17 FunctionalOrganization of the Endocrine System 589

Some ligands bind to membrane-bound receptors,and the

portion ofthe receptor on the inner surface of the plasma mem-

brane acts as an enzyme that adds phosphate groups, a process

called phosphorylation (fos⬘fo¯r-i-la¯⬘shu˘ n),to several specific

proteins. Some of the phosphorylated proteins are part of the

membrane-bound receptor,and others are in the cytoplasm of

the cell (figure 17.21). The phosphorylated proteins influence

the activity ofother enzymes in the cy toplasm of the cell.For ex-

ample,insulin binds to its membrane-bound receptor, resulting

in the phosphorylation of parts of the receptor on the inner sur-

face of the plasma membrane and the phosphorylation of cer-

tain other intracellular proteins. The phosphorylated proteins

produce the responses ofthe cells to insulin. Some receptors for

hormones that phosphorylate intracellular proteins are listed in

table 17.8.

Hormones that stimulate the synthesis of an intracellular

mediator molecule often produce rapid responses.This is possible

because the mediator inﬂuences already-existing enzymes and

causes a cascade effect,which results when a few mediator mole-

cules activate several enzymes and each ofthe activated enzymes in

Epinephrine bound to receptor

in smooth muscle cell

Releases Ca

from

the endoplasmic

reticulum or opens

channels in

the plasma membrane

Response

Regulates enzymes such

as phosphokinases and

increases prostaglandin

synthesis

Phospholipase C

Endoplasmic

reticulum

Diacylglycerol

(DAG)

Phosphoinositol

(PIP

)

Inositol

triphosphate

(IP

)

Response

regulates

enzyme activity

GDP

GTP

Figure 17.19

Membrane-Bound ReceptorsThat Activate G

Proteinsand Increase the Synthesis of IP

and DAG

Epinephrine receptorsin some smooth muscle cells are associated with G

proteins. When epinephrine bindsto the receptor, the G proteins dissociate and

the␣ subunitbinds to GTP. The ␣subunit then binds with phospholipase C,

which actson phosphoinositol (PIP

) and producesinositol triphosphate (IP

)

and diacylglycerol(DAG). IP

releasesCa

2⫹

from the endoplasmicreticulum,

and DAG regulatesenzymes such as those that synthesize prostaglandin

synthesis. These responsesincrease smooth muscle contraction.

Atrial natriuretic

hormone bound

to receptor

GTP

Phosphodiesterase

(inactivates cGMP)

GMP

cGMP

Guanylate

cyclase

Response

Increases Na

excretion by kidney

cells and increases

urine volume

Figure 17.20

Membrane-Bound Receptor ThatDirectly

Synthesizesan Intracellular Mediator

Atrialnatriuretic hormone binds with its receptor site. At the inner surface of

the plasma membrane, guanylylcyclase is activated to produce cGMP from

GTP. CyclicGMP isan intracellular mediator that mediates the response of the

cell. Phosphodiesterase isan enzyme that breaks down cGMP to inactive GMP.

Insulin bound to

the insulin receptor

Active phosphorylase adds

phosphate groups to specific

sites on the receptor and

specific intracellular proteins

PPPP

Figure 17.21

Membrane-Bound ReceptorsThat

Phosphorylate Intracellular Proteins

Insulin receptorsare membrane-bound receptors. When insulin binds to the

insulin receptor, the receptor actsas a phosphorylase enzyme and attaches

phosphate groupsfrom ATP to speciﬁc siteson the receptor and on

intracellular proteins. The phosphorylated proteinsproduce the normal

response to insulin.

Seeley−Stephens−Tate:

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17. Functional Organization

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turn activates several other enzymes that produce the ﬁnal re-

sponse.Thus, an ampliﬁcation system exists in which a few mole-

cules, such as cAMP, cGMP, or phosphorylated proteins, can

control the activity ofmany enzymes within a cell (ﬁgure 17.22)

18. Describe how membrane permeability can be changed

when a hormone bindsto a membrane-bound receptor.

Give an example.

19. Explain how the combination of a ligand and its receptor

can alterthe G proteins on the innersurface of the plasma

Part3 Integration and ControlSystems590

membrane. Which activated subunitof the G protein alters

the activityof molecules inside the plasma membrane or

inside the cell?

20. Describe how G proteins can alter the permeabilityof the

plasma membrane and howthey can alter the synthesisof an

intracellularmediator molecule such ascAMP. Give examples.

21. Other than cAMP and Ca

2ⴙ

, listtwo additional intracellular

mediatorsaffected by G proteins.

Hormone

Receptor

Activated

G proteins

Activated

adenylate

cyclase

Intracellular

Plasma

membrane

cAMP Activated protein

kinase enzymes

Extracellular

Figure 17.22

The Cascade Effect

The combination ofa hormone with a membrane-bound receptor activates severalG proteins. The G proteins, in turn, activate adenylyl cyclase enzymes, which

cause the synthesisof a large number of cAMP molecules. The cAMP molecules, in turn, activate manyprotein kinase enzymes, which produce a rapid and

ampliﬁed response.

Table 17.8

Hormone Source Target Tissue and Effect

Hormones That Bind to Receptors That Phosphorylate Intracellular Proteins

Insulin Pancreatic islets Most cells; increases glucose and amino acid uptake

Growth hormone Anterior pituitary gland Most cells; increases protein synthesis and resists protein breakdown

Prolactin Anterior pituitary gland Mammary glands and ovary; initiates milk production following pregnancy and

helps maintain the corpus luteum

Growth factors Various tissues Stimulate growth in certain cell types

Some intercellular Cells of the immune system Immune-competent cells; help mediate responses of the immune system

immune signal molecules

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Chapter 17 FunctionalOrganization of the Endocrine System 591

22. Describe how a ligand can combine with a membrane-

bound receptorand change enzyme activity inside the cell

and increase phosphorylation of intracellularproteins. Give

examples.

23. What limits the activity of intracellular mediator molecules,

such ascAMP, and phosphorylated proteins?

24. Explain what is meant by the cascade effect for the

intracellularmediator model of hormone action. Does the

intracellularmediator mechanism produce a slowor rapid

response?

PREDICT

When smooth muscle cellsin the airways of the lungscontract, as in

asthma, breathing becomesvery difﬁcult, whereas breathing iseasy if

the smooth muscle cellsare relaxed. During asthma attacks, the

smooth muscle cellsin the airways of the lungscontract. Some of the

drugsused to treat asthma increase cAMP in smooth muscle cells.

Explain asmany ways as possible how these drugsmight work.

Intracellular Hormone Receptors

Objective

■ Explain howligands that cross the plasma membrane can

produce responsesby binding to intracellularreceptors.

Intracellular receptors are either in the cytoplasm or in the

nucleus ofcells. Lipid-soluble ligands cross the plasma membrane

into the cytoplasm or into the nucleus and bind to intracellular re-

ceptors by the process of diffusion (ﬁgure 17.23).After a ligand

binds with an intracellular receptor,the receptor can alter the ac-

tivity ofenzymes in the cell, or it can bind to DNA to produce a re-

sponse (see table 17.4).Some intracellular receptors that inﬂuence

the expression ofDNA are located in the cytoplasm. Once a ligand

binds to its receptor,the receptor and ligand diffuse into the nu-

cleus and bind to DNA.Other intracellular receptors are located in

the nucleus.A ligand diffuses into the nucleus and binds to its re-

ceptor,and the receptor then binds to DNA.

Receptors that interact with DNA have speciﬁc “ﬁngerlike”

projections that interact with speciﬁc parts of a DNA molecule.

The combination ofthe ligand and its receptor with DNA increases

the synthesis of speciﬁc messenger ribonucleic acid (mRNA)

molecules.The mRNA molecules then move to the cytoplasm and

increase the synthesis of speciﬁc proteins at the ribosomes. The

newly synthesized proteins produce the cell response to the ligand.

For example, testosterone from the testes and estrogen from the

ovaries stimulate the synthesis of proteins that are responsible for

the secondary sex characteristics of males and females. The effect

of the steroid aldosterone on its target cells in the kidney is to

1. Aldosterone is a lipid-soluble hormone

and can easily diffuse through the

plasma membrane.

2. Aldosterone, once inside of the cell,

binds with an aldosterone receptor

molecule in the cytoplasm.

3. The aldosterone–receptor complex

moves into the nucleus and binds to

DNA.

6. The proteins synthesized on the

ribosomes produce the response of

the cell to aldosterone.

Aldosterone

Aldosterone–

receptor

complex

Aldosterone

receptor

mRNA synthesis

DNA

mRNA

Plasma

membrane

Nuclear

membrane

Proteins produce

a response.

4. The binding of the aldosterone-

receptor complex to DNA stimulates

the synthesis of messenger RNA

(mRNA) which codes for specific

proteins.

5. The mRNA leaves the nucleus, passes

into the cytoplasm of the cell, and

binds to ribosomes, where it directs the

synthesis of the specific proteins.

mRNA

Ribosome

ProcessFigure 17.23

Intracellular Receptor Model

Seeley−Stephens−Tate:

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17. Functional Organization

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stimulate the synthesis of proteins that increase the rate of Na

⫹

transport. The result is an increase in the reabsorption of Na

⫹

from the ﬁltrate in the kidney and a reduction in the amount of

⫹

lost in the urine. Other hormones that produce responses

through intracellular receptor mechanisms include thyroid hor-

mones and vitamin D (table 17.9).

Cells that synthesize new protein molecules in response to

hormonal stimuli normally have a latent period of several hours

between the time the hormones bind to their receptors and the

time responses are observed.During this latent period, mRNA and

new proteins are synthesized.Receptor–hormone complexes nor-

mally are degraded within the cell,limiting the length of time hor-

mones inﬂuence the activities ofcells, and the cells slowly return to

their previous functional states.

Some cellular functions depend on the coordinated activity

of ligands that bind to membrane-bound receptors and ligands

that bind to intracellular receptors. For example,acetylcholine

molecules, released from nerve cells, bind to membrane-bound

receptors of endothelial cells in blood vessels, and the

combination causes Ca

2⫹

channels to open.The ions then enter

the endothelial cell and activate enzymes that produce nitric oxide

Part3 Integration and ControlSystems592

(NO).NO is a very toxic gas, but in the low concentrations found

in cells,it functions as a ligand. NO diffuses from the endothelial

cells to smooth muscle cells in the blood vessel. It could be

appropriately classiﬁed as a paracrine chemical signal. NO binds

to an intracellular receptor that is part of the enzyme guanylate

cyclase. In response,guanylate cyclase catalyzes the synthesis of

cGMP,which causes the smooth muscle cells to relax (figure

17.24) and blood vessels to dilate.

25. Describe how a ligand that crosses the plasma membrane

interactswith its receptor and how it altersthe rate of

protein synthesis. Whyis there normally a latent period

between the time hormonesbind to their receptors and the

time responsesare observed?

26. What ﬁnally limits the processes activated by the

intracellularreceptormechanism?

PREDICT

Ofmembrane-bound receptors and intracellular receptors, which is

better adapted for mediating a response thatlasts a considerable

length oftime and which is better for mediating a response with a

rapid onsetand a short duration? Explain why.

Table 17.9

Category of

Hormone Hormone Source Target Tissue and Effect

Major Hormones That Combine with Intracellular Receptors

Sex steroids Testosterone Testis Responsible for development of the reproductive structures

and development of male secondary sex characteristics

Progesterone Ovary Causes increased size of cells lining the uterus

Estrogen Ovary Causes increased cell division in the lining of the uterus

Mineralocorticoid Aldosterone Adrenal cortex Increased reabsorption of Na

⫹

and increased secretion

steroids of K

⫹

in the kidney

Glucocorticoid Cortisol Adrenal cortex Increased breakdown of proteins and fats and increased blood

steroid hormones levels of glucose

Thyroid hormones Triiodothyronine (T

) Thyroid gland Regulate development and metabolism

Vitamin D 1,25-dihydroxycholecalciferol Combination of the skin, Increased reabsorption of Ca

2⫹

in the kidney and

liver, and kidney absorption of Ca

2⫹

in the gastrointestinal tract

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Chapter 17 FunctionalOrganization of the Endocrine System 593

Acetylcholine

bound to receptor

Arginine

Extracellular

space

NO synthase

Endothelial cell

of blood vessel

wall

Smooth muscle cell

of blood vessel wall

Guanylate

cyclase

GTP

cGMP Relaxation of smooth

muscle cell

channel

(open)

1. Acetylcholine binds to the

acetylcholine receptor site on

an acetylcholine receptor. The

combination causes a Ca

channel to open, allowing Ca

to diffuse into the endothelial

cell of the blood vessel wall.

2. Ca

binds to a receptor site

on nitric oxide (NO) synthase,

an enzyme that acts on

arginine to produce NO.

3. NO diffuses out of the

endothelial cell and into a

smooth muscle cell of the

blood vessel wall.

4. NO combines with a receptor

site on the enzyme, guanylate

cyclase, which converts GTP to

cGMP. cGMP causes the

smooth muscle cell to relax.

ProcessFigure 17.24

Combined Membrane-Bound and Intracellular Receptor Mechanism

Combination ofa ligand with its membrane-bound receptor resultsin the production of nitric oxide (NO) in one cell (e.g., an endothelial cell of blood vessels). The

NO diffusesinto another cell (e.g., a smooth muscle cell of the blood vessel) and bindsto an intracellular receptor, increasing the synthesis of an intracellular signal

molecule (cAMP), which producesa response (e.g., relaxation of the smooth muscle cells).

GeneralCharacteristics of the

Endocrine System

(p. 572)

1. Endocrine glands produce hormones that are released into the

interstitial ﬂuid,diffuse into the blood, and travel to target tissues,

where they cause a speciﬁc response.

2. Endocrine glands produce other chemical messengers,including

neurohormones,neurotransmitters, neuromodulators,

parahormones,and pheromones.

3. Generalizations about the differences between the endocrine and

nervous systems include the following:(a) the endocrine system is

amplitude-modulated,whereas the nervous system is frequency-

modulated;and (b) the response of target tissues to hormones is

usually slower and oflonger duration than that to neurons.

ChemicalStructure of Hormones

(p. 573)

Hormones are proteins,glycoproteins, polypeptides, derivatives of amino

acids,or lipids (steroids or derivatives of fatty acids).

Controlof Secretion Rate

(p. 573)

1. Most hormones are not secreted at a constant rate.

2. Negative-feedback mechanisms that function to maintain

homeostasis control most hormone secretion.

3. Hormone secretion from an endocrine tissue is regulated by one

ormore of three mechanisms: a nonhormone substance,

stimulation by the nervous system,or a hormone from another

endocrine tissue.

Transportand Distribution in the Body

(p. 578)

Hormones are dissolved in plasma or bind to plasma proteins.The blood

quickly distributes hormones throughout the body.

Metabolism and Excretion

(p. 580)

1. Nonpolar,readily diffusible hormones bind to plasma proteins and

have an increased half-life.

2. Water-soluble hormones,such as proteins,epinephrine, and

norepinephrine,do not bind to plasma proteins or readily diffuse

out ofthe blood. Instead, they are broken down by enzymes or are

taken up by tissues.They have a short half-life.

3. Hormones with a short half-life regulate activities that have a rapid

onset and a short duration.

SUMMARY

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4. Hormones with a long half-life regulate activities that remain at a

constant rate through time.

5. Hormones are eliminated from the blood by excretion from the

kidneys and liver,enzymatic degradation, conjugation,or active

transport.

Interaction ofHormones with

Their TargetTissues

(p. 581)

1. Target tissues have receptor molecules that are speciﬁc for a

particular hormone.

2. Hormones bound with receptors affect the rate at which already

existing processes occur.

3. Down-regulation is a decrease in the number ofreceptor molecules

in a target tissue,and up-regulation is an increase in the number of

receptor molecules.

Classesof Hormone Receptors

(p. 583)

1. Membrane-bound receptors bind to water-soluble or large-

molecular-weight hormones.

2. Intracellular receptors bind to lipid-soluble hormones.

Membrane-Bound Hormone Receptors

1. Membrane-bound receptors are proteins or glycoproteins that have

polypeptide chains that are folded to cross the cell several times.

Part3 Integration and ControlSystems594

2. When a hormone binds to a membrane-bound receptor:

• A change in the structure of membrane channels can result in a

change in permeability ofthe plasma membrane to ions.

• G proteins are activated.The ␣ subunit of the G protein can bind

to ion channels and cause them to open or change the rate of

synthesis ofintracellular mediator molecules, such as cAMP,

cGMP,IP

,and DAG.

• Intracellular enzymes can be directly activated, which in turn

synthesizes intracellular mediators,such as cGMP,or adds a

phosphate group to intracellular enzymes,which alters their

activity.

3. Intracellular mediator mechanisms are rapid-acting because they act

on already-existing enzymes and produce a cascade effect.

Intracellular Hormone Receptors

1. Intracellular receptors are proteins in the cytoplasm or nucleus.

2. Hormones bind with the intracellular receptor,and the

receptor–hormone complex activates genes.Consequently, DNA is

activated to produce mRNA.The mRNA initiates the production of

certain proteins (enzymes) that produce the response ofthe target

cell to the hormone.

3. Intracellular receptor mechanisms are slow-acting because time is

required to produce the mRNA and the protein.

4. Intracellular receptor–activated processes are limited by the

breakdown ofthe receptor–hormone complex.

REVIEW AND COMPREHENSION

1. When comparing the endocrine system and the nervous system,

generally speaking,the endocrine system

a. is faster-acting than the nervous system.

b. produces effects that are of shorter duration.

c. uses amplitude-modulated signals.

d. produces more localized effects.

e. relies less on chemical signals.

2. A chemical signal released from a cell that has a local effect on the

same cell type from which the chemical signal is released is a(n)

a. paracrine chemical signal.

b. pheromone.

c. autocrine chemical signal.

d. hormone.

e. intracellular mediator.

3. Given this list ofmolecule types:

1. nucleic acid derivatives

2. fatty acid derivatives

3. polypeptides

4. proteins

5. phospholipids

Which could be hormone molecules?

a. 1,2,3

b. 2,3,4

c. 1,2,3,4

d. 2,3,4,5

e. 1,2,3,4,5

4. Which ofthese regulates secretion of a hormone from an endocrine

tissue?

a. other hormones

b. negative-feedback mechanisms

c. nonhormone substance in the blood

d. the nervous system

e. all ofthe above

5. Hormones are released into the blood

a. at relatively constant levels.

b. in large amounts in response to a stimulus.

c. increasing and decreasing in a cyclic fashion.

d. all of the above.

6. Lipid-soluble hormones readily diffuse through capillary walls,

whereas water-soluble hormones,such as proteins, must

a. pass through capillary cells.

b. pass through pores in the capillary endothelium.

c. be moved out ofthe capillary by active transport.

d. remain in the blood.

e. be broken down to amino acids before leaving the blood.

7. Concerning the half-life ofhormones,

a. lipid-soluble hormones generally have a longer half-life.

b. hormones with shorter half-lives regulate activities with a slow

onset and long duration.

c. hormones with a shorter half-life are maintained at more

constant levels in the blood.

d. lipid-soluble hormones are degraded rapidly by enzymes in the

circulatory system.

e. water-soluble hormones usually combine with plasma proteins.

8. Given these observations:

1. A hormone will affect only a speciﬁc tissue (not all tissues).

2. A tissue can respond to more than one hormone.

3. Some tissues respond rapidly to a hormone, whereas others take

many hours to respond.

Which ofthese observations can be explained by the characteristics

ofhormone receptors?

a. 1

b. 1,2

c. 2,3

d. 1,3

e. 1,2,3

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9. Which ofthese is not a means by which hormones are eliminated

from the circulatory system?

a. excreted into urine or bile

b. bound to plasma proteins

c. metabolism (enzymatically degraded in the blood)

d. actively transported into cells

e. conjugated with sulfate or glucuronic acid

10. Down-regulation

a. produces a decrease in the number ofreceptors in the target

cells.

b. produces an increase in the sensitivity of the target cells to a

hormone.

c. is found in target cells that respond to hormones that are

maintained at constant levels.

d. occurs partly because of an increase in receptor synthesis by the

target cell.

e. all ofthe above.

11. A ligand

a. can function as an enzyme.

b. is also a G protein.

c. can bind to a receptor site.

d. is an intracellular mediator.

e. all ofthe above.

12. Activated G proteins can

a. cause ion channels to open or close.

b. activate adenylyl cyclase.

c. inhibit the synthesis ofcAMP.

d. alter the activity of IP

e. all ofthe above.

13. Given these events:

1. GTP is converted to GDP.

2. The ␣ subunit separates from the ␤ and␥ units.

3. GDP is released from the ␣ subunit.

List the order in which the events occur after a ligand binds to a

membrane-bound receptor.

a. 1,2,3

b. 1,3,2

c. 2,3,1

d. 3,2,1

e. 3,1,2

14. Which ofthese can limit the response of a cell to a ligand?

a. phosphodiesterase

b. converting GTP to GDP

c. decreasing the number ofreceptors

d. blocking binding sites

e. all ofthe above

15. Given these events:

1. Na

⫹

channels open.

2. Na

⫹

channels close.

3. The plasma membrane depolarizes.

4. The plasma membrane hyperpolarizes.

Choose the arrangement that lists the events in the order they occur

after serotonin binds to its receptor.

a. 1,3

b. 1,4

c. 2,3

d. 2,4

16. Given these events:

1. The ␣ subunit of a G protein interacts with Ca

2⫹

channels.

2. Ca

2⫹

diffuse into the cell.

3. The ␣ subunit of a G protein is activated.

Choose the arrangement that lists the events in the order they occur

after a ligand combines with a receptor on a smooth muscle cell.

a. 1,2,3

b. 1,3,2

c. 2,1,3

d. 3,1,2

e. 3,2,1

17. Given these events:

1. cAMP is synthesized.

2. The ␣ subunit of G protein is activated.

3. Phosphodiesterase breaks down cAMP.

Choose the arrangement that lists the events in the order they occur

after a ligand binds to a receptor.

a. 1,2,3

b. 1,3,2

c. 2,1,3

d. 2,3,1

e. 3,2,1

18. Which ofthese events can occur after a G protein activates

phospholipase C?

a. DAG and IP

are synthesized from PIP

b. I P

causes Ca

2⫹

channels to open.

c. DAG activates enzymes that synthesize prostaglandins.

d. All of the above.

19. When a ligand binds to an intracellular receptor

a. DNA produces mRNA.

b. G proteins are activated.

c. the receptor–hormone complex causes ion channels to open or

close.

d. the cell’s response is faster than when a ligand binds to a

membrane-bound receptor.

e. the ligand is usually a large,water-soluble molecule.

20. Given these events:

1. activation of cAMP

2. activation of genes

3. enzyme activity altered

Which ofthese events can occur when a hormone binds to an

intracellular hormone receptor?

a. 1

b. 1,2

c. 2,3

d. 1,2,3

Answers in Appendix F

Chapter 17 FunctionalOrganization of the Endocrine System 595

Seeley−Stephens−Tate:

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17. Functional Organization

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Part3 Integration and ControlSystems596

ANSWERS TO PREDICT QUESTIONS

1. Because the abnormal substance acts like TSH,it acts on the thyroid

gland to increase the rate ofsecretion of the thyroid hormones, which

increase in concentration in the circulatory system.The thyroid

hormones have a negative-feedback effect on the secretion ofTSH,

thereby decreasing the concentration ofTSH in the circulatory system

to low levels.Because the abnormal substance is not regulated, it can

cause thyroid hormone levels to become very elevated.

2. A major function ofplasma proteins, to which hormones bind,is to

increase the half-life ofthe hormone. If the concentration of the

plasma protein decreases,the half-life and, consequently,the

concentration ofthe hormone in the circulatory system decrease.

The half-life ofthe hormone decreases because the rate hormone

leaves the circulatory system increases.If the secretion rate for the

hormone does not increase,its concentration in the blood declines.

3. Iftoo little estrogen is secreted, the up-regulation of receptors in the

uterus for progesterone cannot occur.As a result,the uterus is not

prepared for the embryo to attach to its wall following ovulation,

and pregnancy cannot occur.Because of the lack of up-regulation,

the uterus probably will not respond to progesterone,regardless of

how much is secreted.If some progesterone receptors are present,

however,the uterus will require a much larger amount of

progesterone to produce the normal response.

4. A drug could increase the cAMP concentration in a cell by

stimulating its synthesis or by inhibiting its breakdown.Drugs that

bind to a receptor that increases adenylate cyclase activity will

increase cAMP synthesis.Because phosphodiesterase normally

causes the breakdown ofcAMP, an inhibitor of phosphodiesterase

decreases the rate ofcAMP breakdown and causes cAMP to increase

in the smooth muscle cells ofthe airway and produces relaxation.

5. Intracellular receptor mechanisms result in the synthesis ofnew

proteins that exist within the cell for a considerable amount oftime.

Intracellular receptors are therefore better adapted for mediating

responses that last a relatively long time (i.e.,for many minutes,

hours,or longer). On the other hand, membrane-bound receptors

that increase the synthesis ofintracellular mediators such as cAMP

normally activate enzymes already existing in the cytoplasm ofthe

cell for shorter periods.The synthesis of cAMP occurs quickly, but

the duration is short because cAMP is broken down quickly,and the

activated enzymes are then deactivated.Membrane-bound receptor

mechanisms are therefore better adapted to short-term and rapid

responses.

Visitthe Online Learning Center at www.mhhe.com/seeley6 for

chapter quizzes, interactive learning exercises, and other studytools.

1. Consider a hormone that is secreted in large amounts at a given

interval,modiﬁed chemically by the liver,and excreted by the kidney at

a rapid rate,thus making the half-life of the hormone in the

circulatory system very short.The hormone therefore rapidly increases

in the blood and then decreases rapidly.Predict the consequences of

liver and kidney disease on the blood levels ofthat hormone.

2. Consider a hormone that controls the concentration ofsome

substance in the circulatory system.If a tumor begins to produce

that substance in large amounts in an uncontrolled fashion,predict

the effect on the secretion rate for the hormone.

3. How could you determine whether or not a hormone-mediated

response resulted from the intracellular mediator mechanism or the

intracellular receptor mechanism?

4. Ifthe effect of a hormone on a target tissue is through a membrane-

bound receptor that has a G protein associated with it,predict the

consequences ifa genetic disease causes the ␣ subunit of the G

protein to have a structure that prevents it from binding to GTP.

5. Prostaglandins are a group ofhormones produced by many cells of

the body.Unlike other hormones,they don’t circulate but usually

have their effect at or very near their site ofproduction.

Prostaglandins apparently affect many body functions,including

blood pressure,inﬂammation, induction of labor, vomiting,fever,

and inhibition ofthe clotting process. Prostaglandins also inﬂuence

the formation ofcAMP. Explain how an inhibitor of prostaglandin

synthesis could be used as a therapeutic agent.Inhibitors of

prostaglandin synthesis can produce side effects.Why?

6. For a hormone that binds to a membrane-bound receptor and has

cAMP as the intracellular mediator,predict and explain the

consequences ifa drug is taken that strongly inhibits

phosphodiesterase.

7. When an individual is confronted with a potentially harmful or

dangerous situation,epinephrine (adrenaline) is released from the

adrenal gland.Epinephrine prepares the body for action by

increasing the heart rate and blood glucose levels.Explain the

advantages or disadvantages associated with a short half-life for

epinephrine and those associated with a long half-life.

8. Thyroid hormones are important in regulating the basal metabolic

rate ofthe body. What are the advantages or disadvantages of

a. a long half-life for thyroid hormones?

b. a short half-life?

9. An increase in thyroid hormones causes an increase in metabolic

rate.If liver disease results in reduced production of the plasma

proteins to which thyroid hormones normally bind,what is the

effect on metabolic rate? Explain.

10. Predict the effect on LH and FSH secretion ifa small tumor in the

hypothalamus ofthe brain secretes large concentrations of GnRH

continuously.Given that LH and FSH regulate the function of the

male and female reproductive systems,predict whether the

condition increases or decreases the activity ofthese systems.

11. Insulin levels normally change in order to maintain normal blood

sugar levels,despite periodic ﬂuctuations in sugar intake. A constant

supply ofinsulin from a skin patch might result in insulin levels that

are too low when blood sugar levels are high (after a meal) and

might be too high when blood sugar levels are low (between meals).

In addition,insulin is a protein hormone that would not readily

diffuse through the lipid barrier ofthe skin (see chapter 5). Estrogen

is a lipid soluble steroid hormone.

Answers in Appendix G

CRITICAL THINKING