Pituitary Hormones and Their Control pdf - Endocrinology and Reproduction

Usually, there is one cell type for each major hormone formed in the

Anterior Pituitary Gland Contains Several Different Cell Types That Synthesize and Secrete

in the body fluids.

excretion into the urine, thus helping to control the concentration of water

The two hormones secreted by the posterior pituitary play other roles.

their hormonal and reproductive activities.

control growth of the ovaries and testes, as well as

luteinizing hormone,

• Two separate gonadotropic hormones,

control the rates of most intracellular chemical reactions in the body.

thyroxine and triiodothyronine by the thyroid gland, and these hormones

Thyroid-stimulating hormone (thyrotropin)

and fats.

adrenocortical hormones, which affect the metabolism of glucose, proteins,

Adrenocorticotropin (corticotropin)

formation, cell multiplication, and cell differentiation.

Growth hormone

Figure 75–2.

roles in the control of metabolic functions throughout the body, as shown in

pituitary. The hormones of the anterior pituitary play major

pituitary, and two important peptide hormones are secreted

itary from the pharyngeal epithelium explains the epithelioid nature of its cells,

neural tissue outgrowth from the hypothalamus. The origin of the anterior pitu-

invagination of the pharyngeal epithelium, and the posterior pituitary from a

Rathke’s pouch,

Embryologically, the two portions of the pituitary originate from different

is much larger and much more functional in some lower animals.

Between these is a small, relatively avascular

neurohypophysis.

posterior pituitary,

adenohypophysis,

pituitary,

logically, the pituitary gland is divisible into two distinct portions: the

) stalk. Physio-

a bony cavity at the base of the brain, and is

hypophysis,

(Figure 75–1), also

The

Pituitary Gland: Two Distinct Parts–The Anterior and Poste-

Pituitary Gland and

Pituitary Hormones and Their

918

Control by the Hypothalamus

Its Relation to the
Hypothalamus

rior Lobes.

pituitary gland

called the

is a small gland—about 1 cen-

timeter in diameter and 0.5 to 1 gram in weight—

that lies in the sella turcica,
connected to the hypothalamus by the pituitary (or hypophysial

anterior

also known as the

and the

also

known as the
zone called the pars intermedia, which is almost absent in the human being but

sources—the anterior pituitary from

which is an embryonic

and the origin of the posterior pituitary from neural tissue explains the pres-
ence of large numbers of glial-type cells in this gland.

Six important peptide hormones plus several less important ones are secreted

by the anterior
by the posterior

•

promotes growth of the entire body by affecting protein

•

controls the secretion of some of the

•

controls the rate of secretion of

• Prolactin promotes mammary gland development and milk production.

follicle-stimulating hormone and

• Antidiuretic hormone (also called vasopressin) controls the rate of water

• Oxytocin helps express milk from the glands of the breast to the nipples

during suckling and possibly helps in the delivery of the baby at the end of
gestation.

Hormones.

and transplanted to some other part of the body, its

thalamus. Indeed, when the pituitary gland is removed

Pituitary Secretion

Hypothalamus Controls

in the chapter.

terior pituitary gland. This is discussed more fully later

of the hypothalamus. The hormones

nocellular neurons,

pituitary gland itself but are large neurons, called

The bodies of the cells that secrete

Posterior Pituitary Hormones Are Synthesized by Cell Bodies in

acidophilic tumors.

Thus, pituitary tumors that

acidophils.

tions, and milk secretion by the breasts.

hormones for controlling thyroid function, sexual func-

cent of the total; nevertheless, they secrete powerful

about 20 per cent are corticotropes that secrete ACTH.

are somatotropes that secrete growth hormone, and

—gonadotropic hormones, which

—adrenocorticotropin (ACTH)

logical actions. These five cell types are:

cell types, the hormones they produce, and their physio-

(Figure 75–3). Table 75–1 provides a summary of these

hormones, at least five cell types can be differentiated

anterior pituitary gland. With special stains attached to

Pituitary Hormones and Their Control by the Hypothalamus

Chapter 75

919

high-affinity antibodies that bind with the distinctive

1. Somatotropes—human growth hormone (hGH)
2. Corticotropes

3. Thyrotropes—thyroid-stimulating hormone (TSH)
4. Gonadotropes

include both luteinizing hormone (LH) and follicle-
stimulating hormone (FSH)

5. Lactotropes—prolactin (PRL)

About 30 to 40 per cent of the anterior pituitary cells

Each of the other cell types accounts for only 3 to 5 per

Somatotropes stain strongly with acid dyes and are

therefore called
secrete large quantities of human growth hormone are
called

the Hypothalamus.

the posterior pituitary hormones are not located in the

mag-

located in the supraoptic and par-

aventricular nuclei
are then transported in the axoplasm of the neurons’
nerve fibers passing from the hypothalamus to the pos-

Almost all secretion by the pituitary is controlled by
either hormonal or nervous signals from the hypo-

from its normal position beneath the hypothalamus

Hypothalamus

Anterior pituitary

Pars intermedia

Posterior pituitary

Hypophysial stalk

Pituitary gland.

Figure 75–1

Thyroid
gland

Mammary
gland

Increases blood

glucose level

Pancreas

Adrenal cortex

Ovary

ACH

Promotes secretion

of insulin

Anterior
pituitary

gland

Thyrotropin

Growth

Corticotropin

Follicle

stimulating

Luteinizing

Prolactin

adrenal corticosteroid hormones.

Metabolic functions of the anterior pituitary hormones. ACH,

Figure 75–2

Sinusoid

Gamma

(

) cell

Alpha

(

) cell

Epsilon (

)

acidophil cell

Delta (

)

basophil cell

Beta (

) cell

Guyton AC: Physiology of the Human Body, 6th ed. Philadelphia:

Cellular structure of the anterior pituitary gland. (Redrawn from

Figure 75–3

Saunders College Publishing, 1984.)

hypothalamus. The blood then flows through small

extensive capillary sinuses among the glandular cells.

The anterior pituitary is a highly vascular gland with

Pituitary Gland

Blood Vessels of the Anterior

pituitary hormones.

of the body, and much of this information is used

thalamus. Thus, the hypothalamus is a collecting center

ents, electrolytes, water, and various hormones in the

the hypothalamus. Even the concentrations of nutri-

the hypothalamus. Olfactory stimuli denoting pleasant

ing thought, a portion of the signal is transmitted into

mitted into the hypothalamus. Likewise, when a

exposed to pain, a portion of the pain signal is trans-

sources in the nervous system. Thus, when a person is

The hypothalamus receives signals from many

cussed in the next section of this chapter.

control their secretion. This system of control is dis-

In the anterior pituitary, these releasing

portal vessels.

in Figure 75–4, to the anterior pituitary through

the hypothalamus itself and then conducted, as shown

and terminate in the posterior pituitary. In contrast,

for prolactin) fall to very low levels.

920

Unit XIV

Endocrinology and Reproduction

rates of secretion of the different hormones (except

Secretion from the posterior pituitary is controlled

by nerve signals that originate in the hypothalamus

secretion by the anterior pituitary is controlled by hor-
mones called hypothalamic releasing and hypothala-
mic inhibitory hormones (or factors) secreted within

minute blood vessels called hypothalamic-hypophysial

and inhibitory hormones act on the glandular cells to

person experiences some powerful depressing or excit-

or unpleasant smells transmit strong signal compo-
nents directly and through the amygdaloid nuclei into

blood excite or inhibit various portions of the hypo-

for information concerning the internal well-being

to control secretions of the many globally important

Hypothalamic-Hypophysial Portal

Almost all the blood that enters these sinuses passes
first through another capillary bed in the lower

Table 75–1

IGF, insulin-like

Mammotropes

acids

Lactotropes,

Prolactin (PRL)

Single chain of 198 amino

Stimulates milk secretion and production

by the ovary; stimulates testosterone

(115 amino acids)

production of estrogen and progesterone

(89 amino acids) and

corpus luteum in the ovary; stimulates

Luteinizing hormone (LH)

Glycoprotein of two subunits,

Causes ovulation and formation of the

(112 amino acids)

the testis

(89 amino acids) and

follicles; regulates spermatogenesis in

Gonadotropes

Follicle-stimulating hormone

Glycoprotein of two subunits,

Stimulates development of ovarian

(112 amino acids)

maintains size of follicular cells

(89 amino acids) and

hormones by thyroid follicular cells;

(TSH; thyrotropin)

Thyrotropes

Thyroid-stimulating hormone

Glycoprotein of two subunits,

Stimulates production of thyroid

(ACTH; corticotropin)

and androgens by the adrenal cortex;

Corticotropes

Adrenocorticotropic hormone

Single chain of 39 amino acids

Stimulates production of glucocorticoids

somatotropin)

secretion of IGF-1; stimulates lipolysis;

Somatotropes

Growth hormone (GH;

Single chain of 191 amino acids

Stimulates body growth; stimulates

Cell

Hormone

Chemistry

Physiological Actions

Cells and Hormones of the Anterior Pituitary Gland and Their Physiological Functions

inhibits actions of insulin on
carbohydrate and lipid metabolism

maintains size of zona fasciculata and
zona reticularis of cortex

a
b

(FSH)

a
b

production by the testis

growth factor

Median eminence

Optic chiasm

Artery

Primary capillary
plexus

Hypothalamic-
hypophysial
portal vessels

Sinuses

Anterior pituitary
gland

Vein

Posterior pituitary

gland

Mamillary body

Hypothalamus

Hypothalamic-hypophysial portal system.

Figure 75–4

along with the target glands. Growth hormone, in

tive target glands that, except for growth hormone,

cortex, ovaries, testicles, and mammary glands. The

ulating target glands, including thyroid gland, adrenal

growth hormone, exert their principal effects by stim-

All the major anterior pituitary hormones, except for

of Growth Hormone

misleading to attempt delineation here.

hormones are still poorly known, so that it would be

The specific loci of the neuronal cell bodies that form

hypothalamic hormones. However, the neuronal cell

and, therefore, causes release of essentially all the

transported to the anterior pituitary gland. Electrical

cific Hypothalamic Releasing and Inhibitory Hormones.

Specific Areas in the Hypothalamus Control Secretion of Spe-

this and subsequent chapters.

itary hormones. Each of the more important hypo-

There are some additional hypothalamic hormones,

(PIH), which causes

causes release of the two gonadotropic hormones,

(GnRH), which

(GHIH), also

growth hormone inhibitory hormone

which causes release of growth hormone, and

Growth hormone–releasing hormone

(CRH), which

(TRH), which

summarized in Table 75–2 and are the following:

hormone probably exerts more control. The major

important, but for prolactin, a hypothalamic inhibitory

itary hormones, it is the releasing hormones that are

rior pituitary hormones. For most of the anterior pitu-

The function of the releasing and

rior Pituitary Secretion.

Hypothalamic Releasing and Inhibitory Hormones Control Ante-

These hormones are immediately absorbed into the

ing and inhibitory hormones into the tissue fluids.

endings in the central nervous system, in that their

The endings of these fibers are different from most

tion of the anterior pituitary hormones. These neurons

Hypothalamic Releasing and Inhibitory Hormones Are Secreted

blood to the anterior pituitary sinuses.

hypothalamic-hypophysial portal blood vessels. These

vessels return to its surface, coalescing to form the

stalk. Small arteries penetrate into the substance

eminence,

ermost portion of the hypothalamus, called the

anterior pituitary sinuses. Figure 75–4 shows the low-

Pituitary Hormones and Their Control by the Hypothalamus

Chapter 75

921

hypothalamic-hypophysial portal blood vessels into the

median

which connects inferiorly with the pituitary

of the median eminence and then additional small

pass downward along the pituitary stalk to supply

into the Median Eminence.

Special neurons in the hypo-

thalamus synthesize and secrete the hypothalamic
releasing and inhibitory hormones that control secre-

originate in various parts of the hypothalamus and
send their nerve fibers to the median eminence and
tuber cinereum, an extension of hypothalamic tissue
into the pituitary stalk.

function is not to transmit signals from one neuron to
another but rather to secrete the hypothalamic releas-

hypothalamic-hypophysial portal system and carried
directly to the sinuses of the anterior pituitary gland.

inhibitory hormones is to control secretion of the ante-

hypothalamic releasing and inhibitory hormones are

1. Thyrotropin-releasing hormone

causes release of thyroid-stimulating hormone

2. Corticotropin-releasing hormone

causes release of adrenocorticotropin

(GHRH),

called somatostatin, which inhibits release of
growth hormone

4. Gonadotropin-releasing hormone

luteinizing hormone and follicle-stimulating
hormone

5. Prolactin inhibitory hormone

inhibition of prolactin secretion

including one that stimulates prolactin secretion and
perhaps others that inhibit release of the anterior pitu-

thalamic hormones is discussed in detail as the specific
hormonal systems controlled by them are presented in

All or

most of the hypothalamic hormones are secreted at
nerve endings in the median eminence before being

stimulation of this region excites these nerve endings

bodies that give rise to these median eminence nerve
endings are located in other discrete areas of the hypo-
thalamus or in closely related areas of the basal brain.

the different hypothalamic releasing or inhibitory

Physiological Functions

functions of each of these pituitary hormones are so
intimately concerned with the functions of the respec-

their functions are discussed in subsequent chapters

Table 75–2

Prolactin-inhibiting hormone (PIH)

Dopamine (a catecholamine)

Inhibits secretion of prolactin by lactotropes

Growth hormone inhibitory hormone

Single chain of 14 amino acids

Inhibits secretion of growth hormone by somatotropes

Growth hormone–releasing hormone

Single chain of 44 amino acids

Stimulates secretion of growth hormone by somatotropes

Corticotropin-releasing hormone (CRH)

Single chain of 41 amino acids

Stimulates secretion of ACTH by corticotropes

Gonadotropin-releasing hormone (GnRH)

Single chain of 10 amino acids

Stimulates secretion of FSH and LH by gonadotropes

Thyrotropin-releasing hormone (TRH)

Peptide of 3 amino acids

Stimulates secretion of TSH by thyrotropes

Hormone

Structure

Primary Action on Anterior Pituitary

Hypothalamic Releasing and Inhibitory Hormones That Control Secretion of the Anterior Pituitary Gland

(GHRH)

(somatostatin)

ACTH, adrenocorticotropic hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone.

for Energy

Growth Hormone Enhances Fat Utilization

proteins.

of amino acid uptake and protein synthesis by cells,

Summary.

sparer.”

for the body’s cells, thus acting as a potent “protein

tissue, and these are used to supply most of the energy

decrease in the breakdown of cell protein. A probable

tion to the increase in protein synthesis, there is a

tion of growth hormone.

In the long run, this may be the most important func-

vitamins, and other requisites for growth are available.

and promotes growth if sufficient energy, amino acids,

tities of RNA. This promotes more protein synthesis

the nucleus, causing the formation of increased quan-

hormone also stimulates the transcription of DNA in

more prolonged periods (24 to 48 hours), growth

Increased Nuclear Transcription of DNA to Form RNA.

cytoplasm.

still increases RNA translation, causing protein to be

tions are not increased in the cells, growth hormone

Enhancement of RNA Translation to Cause Protein Synthesis by

trolling glucose transport through the membrane, as

the increased protein synthesis. This control of amino

the cell membranes to the interior of the cells. This

Enhancement of Amino Acid Transport Through the Cell Mem-

a series of different effects are known, all of which

Growth Hormone Promotes Protein Deposition

serves carbohydrates.

enhances body protein, uses up fat stores, and con-

throughout the body. Thus, in effect, growth hormone

energy; and (3) decreased rate of glucose utilization

acids in the blood, and increased use of fatty acids for

fatty acids from adipose tissue, increased free fatty

most cells of the body; (2) increased mobilization of

hormone has multiple specific metabolic effects,

Aside from its general effect in causing growth, growth

Metabolic Effects

the body can continue to grow throughout life.

bone cannot occur, even though most other tissues of

have united with the shafts, further lengthening of

many of the soft tissues continued to grow. This results

reached, most of the bones stopped lengthening, but

increased proportionately in size; after adulthood was

stages of development, all organs of the treated rat

after the two rats reached adulthood. In the early

did not receive growth hormone. This figure shows

growing littermate rats, one of which received daily

Figure 75–5 shows typical weight charts of two

such as bone growth cells and early muscle cells.

mitosis, with development of greater numbers of cells

all tissues of the body that are capable of growing. It

molecular weight of 22,005. It causes growth of almost

Growth hormone, also called

of Many Body Tissues

almost all tissues of the body.

contrast to other hormones, does not function through

922

Unit XIV

Endocrinology and Reproduction

a target gland but exerts its effects directly on all or

Growth Hormone Promotes Growth

somatotropic hormone

or somatotropin, is a small protein molecule that con-
tains 191 amino acids in a single chain and has a

promotes increased sizes of the cells and increased

and specific differentiation of certain types of cells

injections of growth hormone and the other of which

marked enhancement of growth in the rat given
growth hormone—in the early days of life and even

from the fact that once the epiphyses of the long bones

Growth Hormone Has Several

including (1) increased rate of protein synthesis in

in Tissues

Although the precise mechanisms by which growth
hormone increases protein deposition are not known,

could lead to enhanced protein deposition.

branes.

Growth hormone directly enhances transport

of at least some and perhaps most amino acids through

increases the amino acid concentrations in the cells
and is presumed to be at least partly responsible for

acid transport is similar to the effect of insulin in con-

discussed in Chapters 67 and 78.

the Ribosomes.

Even when the amino acid concentra-

synthesized in greater amounts by the ribosomes in the

Over

Decreased Catabolism of Protein and Amino Acids.

In addi-

reason for this is that growth hormone also mobilizes
large quantities of free fatty acids from the adipose

Growth hormone enhances almost all facets

while at the same time reducing the breakdown of

Growth hormone has a specific effect in causing
the release of fatty acids from adipose tissue and,

600

Control

Injected daily with

growth hormone

500

400

300

200

500

400

300

200

100

Body weight (grams)

Days

hormone with that of a normal littermate.

Comparison of weight gain of a rat injected daily with growth

Figure 75–5

chondrocytes cultured outside the body, proliferation

When growth hormone is supplied directly to cartilage

of Its Effect Through Intermediate

eyes.

lower teeth. Likewise, the bones of the skull can grow

lescence, causing forward protrusion of the chin and

cially true for the membranous bones. For instance, the

under the influence of growth hormone; this is espe-

Therefore, the

hormone strongly stimulates osteoblasts.

Growth

resorption, the thickness of the bone increases.

When the rate of deposition is greater than that of

(discussed in detail in Chapter 79) remove old bone.

of older bone. Simultaneously,

further lengthening of the long bone can occur.

the shaft and the epiphysis at each end, so that no

bone growth. At this time, bony fusion occurs between

used up, so that by late adolescence, no additional epi-

time, the epiphyseal cartilage itself is progressively

the epiphyses farther and farther apart. At the same

into new bone, thus elongating the shaft and pushing

deposition of new cartilage, followed by its conversion

are separated from the shaft. This growth first causes

cartilages, where the epiphyses at the ends of the bone

tion, the long bones grow in length at the epiphyseal

growth. First, in response to growth hormone stimula-

There are two principal mechanisms of bone

bone.

into osteogenic cells, thus causing deposition of new

and (3) a specific effect of converting chondrocytes

(2) increased rate of reproduction of these cells,

cytic and osteogenic cells that cause bone growth,

multiple effects of growth hormone on bone, including

increase growth of the skeletal frame. This results from

all tissues of the body, its most obvious effect is to

enhance the transport of some amino acids into cells,

well. Especially important is insulin’s ability to

olism of growth, but there seem to be other effects as

tive. Part of this requirement for carbohydrates and

excluded from the diet. This shows that adequate

creas; it also fails to cause growth if carbohydrates are

and skeletal muscle to insulin’s effects on carbohy-

tissue glucose utilization. Experimental studies indi-

trations of fatty acids may impair insulin’s actions on

decreased glucose utilization by the cells. However,

We do not know the precise mechanism by which

dependent) diabetes, who are also very resistant to the

diabetogenic,

For these reasons, growth hormone’s effects are called

liver; this leads to increased blood glucose concentra-

ates insulin’s actions to stimulate the uptake and uti-

hormone–induced “insulin resistance,” which attenu-

the liver, and (3) increased insulin secretion.

muscle and fat, (2) increased glucose production by

influence carbohydrate metabolism, including (1)

Growth Hormone Decreases

liver.

This excessive mobilization of fat

ketosis.

formed by the liver and released into the body fluids,

ence of excessive amounts of growth hormone, fat

in minutes under the influence of growth hormone.

fat by growth hormone requires several hours to occur,

increase in lean body mass. However, mobilization of

together with its protein anabolic effect, causes an

Growth hormone’s ability to promote fat utilization,

proteins.

the influence of growth hormone, fat is used for

subsequent utilization for energy. Therefore, under

fatty acids to acetyl coenzyme A (acetyl-CoA) and its

body, growth hormone enhances the conversion of

the body fluids. In addition, in tissues throughout the

therefore, increasing the concentration of fatty acids in

Pituitary Hormones and Their Control by the Hypothalamus

Chapter 75

923

energy in preference to the use of carbohydrates and

whereas enhancement of protein synthesis can begin

“Ketogenic” Effect of Growth Hormone.

Under the influ-

mobilization from adipose tissue sometimes becomes
so great that large quantities of acetoacetic acid are

thus causing
from the adipose tissue also frequently causes a fatty

Carbohydrate Utilization

Growth hormone causes multiple effects that

decreased glucose uptake in tissues such as skeletal

Each of these changes results from growth

lization of glucose in skeletal muscle and fat and to
inhibit gluconeogenesis (glucose production) by the

tion and a compensatory increase in insulin secretion.

and excess secretion of growth hormone

can produce metabolic disturbances very similar to
those found in patients with type II (non-insulin-

metabolic effects of insulin.

growth hormone causes insulin resistance and

growth hormone–induced increases in blood concen-

cate that raising blood levels of fatty acids above
normal rapidly decreases the sensitivity of the liver

drate metabolism.

Necessity of Insulin and Carbohydrate for the Growth-
Promoting Action of Growth Hormone.

Growth hormone

fails to cause growth in an animal that lacks a pan-

insulin activity and adequate availability of carbohy-
drates are necessary for growth hormone to be effec-

insulin is to provide the energy needed for the metab-

in the same way that it stimulates glucose transport.

Growth Hormone Stimulates Cartilage
and Bone Growth

Although growth hormone stimulates increased de-
position of protein and increased growth in almost

(1) increased deposition of protein by the chondro-

physeal cartilage remains to provide for further long

Second, osteoblasts in the bone periosteum and in

some bone cavities deposit new bone on the surfaces

osteoclasts in the bone

bones can continue to become thicker throughout life

jaw bones can be stimulated to grow even after ado-

in thickness and give rise to bony protrusions over the

Growth Hormone Exerts Much

Substances Called “Somatomedins”
(Also Called “Insulin-Like
Growth Factors”)

For instance, the extremely high levels of growth

depletion than with the degree of glucose insufficiency.

chronic conditions, growth hormone secretion seems

an acute decrease in protein intake. Conversely, in

Under acute conditions, hypoglycemia is a far more

child or adolescent, it is about 6 ng/ml. These values

plasma of an adult is between 1.6 and 3 ng/ml; in a

The normal concentration of growth hormone in the

shown in Figure 75–6. Table 75–3 summarizes some of

deep sleep,

exercise;

low concentration of

secretion: (1)

understood, but several factors related to a person’s

increasing and decreasing. The precise mechanisms

per cent of the adolescent level in very old age.

decreases slowly with aging, finally falling to about 25

has proved to be untrue. After adolescence, secretion

then disappeared from the blood at adolescence. This

For many years it was believed that growth hormone

Figure 75–6.

This greatly prolongs the growth-promoting effects of

blood to the tissues, with a half-time of about 20 hours.

result, somatomedin C is released only slowly from the

is produced in response to growth hormone. As a

carrier protein in the blood that, like somatomedin C,

By contrast, somatomedin C attaches strongly to a

having a half-time in the blood of less than 20 minutes.

it is released from the blood into the tissues rapidly,

weakly to the plasma proteins in the blood. Therefore,

one.

local tissue to cause local growth. It is also possible

of the somatomedin hypothesis are still questionable.

hormone required for this is minute. Some aspects

of these cartilage areas, and the amount of growth

bones and other peripheral tissues. Even so, experi-

somatomedin C and other somatomedins, rather

It has been postulated that most, if not all, of the

people. Some other dwarfs (e.g., the Lévi-Lorain

growth hormone is either normal or high, they have

Therefore, even though their plasma concentration of

synthesize significant amounts of somatomedin C.

The pygmies of Africa have a congenital inability to

somatomedin C is about 7500, and its concentration in

(also called IGF-I). The molecular weight of

effects of insulin on growth. Therefore, the somato-

increasing all aspects of bone growth. Many of the

causes the liver (and, to a much less extent,

In brief, it has been found that growth hormone

same cells.

occur. Yet growth hormone injected into the intact

or enlargement of the chondrocytes usually fails to

924

Unit XIV

Endocrinology and Reproduction

animal does cause proliferation and growth of the

other tissues) to form several small proteins
called somatomedins that have the potent effect of

somatomedin effects on growth are similar to the

medins are also called insulin-like growth factors
(IGFs).

At least four somatomedins have been isolated,

but by far the most important of these is somatomedin
C

the plasma closely follows the rate of growth hormone
secretion.

diminished amounts of somatomedin C in the plasma;
this apparently accounts for the small stature of these

dwarf) also have this problem.

growth effects of growth hormone result from

than from direct effects of growth hormone on the

ments have demonstrated that injection of growth
hormone directly into the epiphyseal cartilages of
bones of living animals causes the specific growth

One possibility is that growth hormone can cause
the formation of enough somatomedin C in the

that growth hormone itself is directly responsible
for increased growth in some tissues and that the
somatomedin mechanism is an alternative means of
increasing growth but not always a necessary

Short Duration of Action of Growth Hormone but Prolonged
Action of Somatomedin C.

Growth hormone attaches only

the bursts of growth hormone secretion shown in

Regulation of Growth
Hormone Secretion

was secreted primarily during the period of growth but

Growth hormone is secreted in a pulsatile pattern,

that control secretion of growth hormone are not fully

state of nutrition or stress are known to stimulate

starvation, especially with severe protein

deficiency; (2) hypoglycemia or
fatty acids in the blood; (3)

(4) excitement; and

(5) trauma. Growth hormone also characteristically
increases during the first 2 hours of

the factors that are known to influence growth
hormone secretion.

often increase to as high as 50 ng/ml after depletion of
the body stores of proteins or carbohydrates during
prolonged starvation.

potent stimulator of growth hormone secretion than is

to correlate more with the degree of cellular protein

hormone that occur during starvation are closely
related to the amount of protein depletion.

8 am

4 am 8 pm

4 am

Noon

Midnight

8 am

Growth hormone

(ng/ml plasma)

Strenuous
exercise

Sleep

and also the high rate of growth hormone secretion that occurs

demonstrating the especially powerful effect of strenuous exercise

Typical variations in growth hormone secretion throughout the day,

Figure 75–6

during the first few hours of deep sleep.

and release of the hormone into the blood. The long-

cell; within minutes, this causes fusion of the growth

both a short-term and a long-term effect. The short-

cyclic adenosine monophosphate (cAMP). This has

the cell membrane, increasing the intracellular level of

receptors activate the adenylyl cyclase system inside

of the growth hormone cells in the pituitary gland. The

through the inhibitory hormone somatostatin. GHRH

a different neuronal system in the hypothalamus, all

dopamine, and serotonin, each of which is released by

experiments have shown that catecholamines,

mic control of growth hormone secretion. In fact,

emotions, stress, and trauma can all affect hypothala-

In a similar manner, hypothalamic signals depicting

person’s behavioral feeding instincts also alter the rate

areas of the hypothalamus. Therefore, it is reasonable

glycemic states and hunger in hypoglycemic states. The

blood glucose concentration, causing satiety in hyper-

of GHRH is the ventromedial nucleus; this is the

The part of the hypothalamus that causes secretion

amino acids.

amino acids, and somatostatin is composed of 14

these are polypeptides; GHRH is composed of 44

). Both of

growth hormone

growth

hypophysial portal vessels.

They are

growth hormone secretion. It is known that growth

that can affect growth hormone secretion, one can

From the preceding description of the many factors

Hormone Secretion

Somatostatin in the Control of Growth

Hormone–Releasing Hormone, and

Role of the Hypothalamus, Growth

growth hormone. The protein deficiency must also be

tions of protein malnutrition, adequate calories alone

These results demonstrate that under severe condi-

tant decrease in the hormone.

ments for 3 and 25 days, respectively, with a concomi-

hormone concentration. The third and fourth columns

of carbohydrates in their diets, demonstrating that

extreme protein deficiency during the protein malnu-

of adding protein to the diet. The first column shows

ciency on plasma growth hormone and then the effect

Figure 75–7 demonstrates the effect of protein defi-

Pituitary Hormones and Their Control by the Hypothalamus

Chapter 75

925

very high levels of growth hormone in children with

trition condition called kwashiorkor; the second
column shows the levels in the same children after 3
days of treatment with more than adequate quantities

the carbohydrates did not lower the plasma growth

show the levels after treatment with protein supple-

are not sufficient to correct the excess production of

corrected before the growth hormone concentration
will return to normal.

readily understand the perplexity of physiologists as
they attempt to unravel the mysteries of regulation of

hormone secretion is controlled by two factors
secreted in the hypothalamus and then transported to
the anterior pituitary gland through the hypothalamic-

hormone–releasing hormone and
inhibitory hormone (also called somatostatin

same area of the hypothalamus that is sensitive to

secretion of somatostatin is controlled by other nearby

to believe that some of the same signals that modify a

of growth hormone secretion.

increase the rate of growth hormone secretion.

Most of the control of growth hormone secretion

is probably mediated through GHRH rather than

stimulates growth hormone secretion by attaching to
specific cell membrane receptors on the outer surfaces

term effect is to increase calcium ion transport into the

hormone secretory vesicles with the cell membrane

term effect is to increase transcription in the nucleus

Table 75–3

Factors That Stimulate or Inhibit Secretion of

Growth hormone–releasing

growth factors)

Deep sleep ( stages II and IV)

Somatomedins (insulin-like

Testosterone, estrogen

Growth hormone (exogenous)

Exercise

hormone (somatostatin)

Trauma, stress, excitement

Growth hormone inhibitory

deficiency

Obesity

Starvation or fasting, protein

Aging

acids

Decreased blood free fatty

Increased blood free fatty

Decreased blood glucose

Increased blood glucose

Secretion

Stimulate Growth Hormone

Inhibit Growth Hormone

Growth Hormone

hormone

Protein

deficiency

(kwashiorkor)

Protein

treatment
(25 days)

Protein

treatment

(3 days)

Carbohydrate

treatment

(3 days)

Plasma growth hormone (ng/ml)

on growth hormone secretion in protein-calorie malnutrition. Am J

treatment in lowering growth hormone concentration. (Drawn from

failure of carbohydrate treatment but the effectiveness of protein

of growth hormone in the disease kwashiorkor. Also shown is the

Effect of extreme protein deficiency on the plasma concentration

Figure 75–7

data in Pimstone BL, Barbezat G, Hansen JD, Murray P: Studies

Clin Nutr 21:482, 1968.)

diagnosed, further effects can often be blocked by

death in early adulthood. However, once gigantism is

general deficiency of pituitary hormones usually causes

grows until the gland itself is destroyed. This eventual

ops if they remain untreated, because the gigantism is

In most giants, panhypopituitarism eventually devel-

ally develops.

per cent of giants, full-blown

owing to the hyperglycemia. Consequently, in about 10

The giant ordinarily has

the long bones have become fused with the shafts,

tion occurs before adolescence, before the epiphyses of

tissues grow rapidly, including the bones. If the condi-

quantities of growth hormone are produced. All body

dophilic tumors occur in the gland. As a result, large

become excessively active, and sometimes even aci-

Occasionally,

the acidophilic,

growth

and thyroid hormones.

abnormal sexual functions, the patient can usually be

mones) and has lost all sexual functions. Except for the

adrenocorticotropic, adrenocortical, and thyroid hor-

functions are lost. Thus, the picture is that of a lethargic

corticoids by the adrenal glands, and (3) suppressed

(1) hypothyroidism, (2) depressed production of gluco-

The general effects of adult panhypopituitarism are

birth of her baby.

blood vessels. This abnormality occasionally occurs

destroyed. The third cause is thrombosis of the pituitary

craniopharyngiomas or chromophobe tumors, may

three common abnormalities. Two tumorous conditions,

because of its widespread metabolic functions.

cured if treated early in life. Human growth hormone

pure growth hormone deficiency can be completely

quantities for treatment purposes. Dwarfs who have

Therefore, this hormone is now available in sufficient

ful application of recombinant DNA technology.

Escherichia coli

However, human growth hormone can now be synthe-

hormone deficiency, except on an experimental basis.

pared from human pituitary glands, it was difficult to

In the past, because growth hormone had to be pre-

to distinguish it from the others.

human growth

is not effective in human beings. Therefore, the growth

lower animals (except, to some extent, from primates)

species. For this reason, growth hormone prepared from

only in the one species or, at most, closely related

Treatment with Human Growth Hormone.

of growth by growth hormone.

somatomedin C, which is a key step for the promotion

or high, but there is a hereditary inability to form

dwarf), the rate of growth hormone secretion is normal

of dwarfism (the African pygmy and the Lévi-Lorain

mature sexually and occasionally reproduce. In one type

only growth hormone is deficient; these persons do

sexual functions. In one third of such dwarfs, however,

10 years.

aged 4 to 5 years, and the same person at age 20 years

greatly decreased. A child who has reached the age of

portion to one another, but the rate of development is

popituitarism) during childhood. In general, all the

alized deficiency of anterior pituitary secretion (panhy-

may occur suddenly or slowly at any time during life,

secretion may be congenital (present from birth), or it

of all the anterior pituitary hormones. The decrease in

This term means decreased secretion

Abnormalities of Growth

cells.

growth hormone secretion. Growth hormone, in turn,

need for cellular proteins—for instance, after a severe

nutrition. That is, nutritional deficiency or excess tissue

tissues themselves, especially their level of protein

ing: the major long-term controller of growth hormone

thesis and tissue growth, we can propose the follow-

a composite picture. Yet, because of the extreme secre-

In summary, our knowledge of the regulation of

tion, are uncertain.

somatostatin, which inhibits growth hormone secre-

for essentially all hormones. The nature of this feed-

subject to typical negative feedback control, as is true

This demonstrates that growth hormone secretion is

of endogenous growth hormone secretion decreases.

the blood of an animal over a period of hours, the rate

When growth hormone is administered directly into

hormone.

926

Unit XIV

Endocrinology and Reproduction

by the genes to stimulate the synthesis of new growth

back mechanism and whether it is mediated mainly
through inhibition of GHRH or enhancement of

growth hormone secretion is not sufficient to describe

tion of growth hormone during starvation and its
important long-term effect to promote protein syn-

secretion is the long-term state of nutrition of the

bout of exercise when the muscles’ nutritional status
has been taxed—in some way increases the rate of

promotes synthesis of new proteins while at the same
time conserving the proteins already present in the

Hormone Secretion

Panhypopituitarism.

most often resulting from a pituitary tumor that
destroys the pituitary gland.

Dwarfism.

Most instances of dwarfism result from gener-

physical parts of the body develop in appropriate pro-

10 years may have the bodily development of a child

may have the bodily development of a child aged 7 to

A person with panhypopituitary dwarfism does not

pass through puberty and never secretes sufficient
quantities of gonadotropic hormones to develop adult

Growth hor-

mones from different species of animals are sufficiently
different from one another that they will cause growth

hormone of the human being is called
hormone

obtain sufficient quantities to treat patients with growth

sized by

bacteria as a result of success-

may prove to be beneficial in other metabolic disorders

Panhypopituitarism in the Adult.

Panhypopituitarism first

occurring in adulthood frequently results from one of

compress the pituitary gland until the functioning
anterior pituitary cells are totally or almost totally

when a new mother develops circulatory shock after the

secretion of the gonadotropic hormones so that sexual

person (from lack of thyroid hormones) who is gaining
weight (because of lack of fat mobilization by growth,

treated satisfactorily by administering adrenocortical

Gigantism.

hormone–producing cells of the anterior pituitary gland

height increases so that the person becomes a giant—
up to 8 feet tall.

hyperglycemia, and the beta

cells of the islets of Langerhans in the pancreas are
prone to degenerate because they become overactive

diabetes mellitus eventu-

usually caused by a tumor of the pituitary gland that

microsurgical removal of the tumor or by irradiation of
the pituitary gland.

oxytocin.

(ADH), also

hormones: (1)

capillaries, where they secrete two posterior pituitary

secretory granules. These endings lie on the surfaces of

(hypophysial stalk). The

in Figure 75–9. These tracts pass to the neurohypoph-

of the hypothalamus, as shown

The pituicytes do not secrete hormones; they

pituicytes.

pophysis,

The

Posterior Pituitary Gland

of increased energy.

the muscles; (2) decreased fat deposits; and (3) a feeling

increased protein deposition in the body, especially in

important effects that suggest antiaging actions: (1)

secretion. In fact, multiple tests of growth hormone

Thus, it is highly possible that some of the normal

As one ages, the average plasma concentration of

function of some of the organs, and diminished muscle

increased wrinkling of the skin, diminished rates of

its place. The physical and physiological effects are

ance of a person aged 65. The aged appearance seems

For instance, a 50-year-old person who has been without

hormone, some features of the aging process accelerate.

kidneys, become greatly enlarged.

organs, such as the tongue, the liver, and especially the

Finally, many soft tissue

kyphosis.

vertebrae ordinarily cause a hunched back, which is

normal size. In addition to these effects, changes in the

require size 14 or larger shoes, and the fingers become

nose increases to as much as twice normal size, the feet

excess development of the supraorbital ridges, the

half an inch, the forehead slants forward because of

the lower jaw protrudes forward, sometimes as much as

growth does not cease at adolescence. Consequently,

jawbone, and portions of the vertebrae, because their

nose, bosses on the forehead, supraorbital ridges, lower

membranous bones,

acromegaly.

Figure 75–8, is known as

tissues can continue to grow. This condition, shown in

taller, but the bones can become thicker and the soft

cence—that is, after the epiphyses of the long bones

Acromegaly.

Pituitary Hormones and Their Control by the Hypothalamus

Chapter 75

927

If an acidophilic tumor occurs after adoles-

have fused with the shafts—the person cannot grow

Enlargement is

especially marked in the bones of the hands and feet
and in the

including the cranium,

extremely thickened so that the hands are almost twice

known clinically as

Possible Role of Decreased Growth Hormone Secretion
in Causing Changes Associated with Aging

In people who have lost the ability to secrete growth

growth hormone for many years may have the appear-

to result mainly from decreased protein deposition in
most tissues of the body and increased fat deposition in

mass and strength.

growth hormone in an otherwise normal person
changes approximately as follows:

aging effects result from diminished growth hormone

therapy in older people have demonstrated three

and Its Relation to the
Hypothalamus

posterior pituitary gland, also called the neurohy-

is composed mainly of glial-like cells called

act simply as a supporting structure for large numbers
of terminal nerve fibers and terminal nerve endings
from nerve tracts that originate in the supraoptic and
paraventricular nuclei

ysis through the pituitary stalk
nerve endings are bulbous knobs that contain many

antidiuretic hormone

called vasopressin, and (2)

Acromegalic patient.

Figure 75–8

20 to 40 years

5 to 20 years

ng/ml

40 to 70 years

1.6

a few minutes.

small amounts to large amounts, or vice versa, in only

centration of ADH in the body fluids can change from

almost total cessation of ADH secretion.Thus, the con-

Conversely, injection of a dilute solution into this

ing the ADH secretion to as high as 20 times normal.

of ADH into the circulating blood, sometimes increas-

hypothalamus, the ADH neurons in the supraoptic and

When a concentrated electrolyte

Regulation of ADH Production

mechanism of the kidneys.

lecting tubules and ducts by osmosis, as explained in

interstitial fluid. Water is then absorbed from the col-

process reverses in another 5 to 10 minutes. Thus, this

minutes. Then, in the absence of ADH, the entire

water permeability. All this occurs within 5 to 10

cell membranes, thus providing many areas of high

phosphorylation of elements in the special vesicles,

of cAMP inside the tubular cell cytoplasm. This causes

that activate adenylyl cyclase and cause the formation

on the cell, it first combines with membrane receptors

When ADH acts

aquaporins.

number of special vesicles that have highly water-

ducts are almost impermeable to water. However,

partially known. Without ADH, the luminal mem-

The precise mechanism by which ADH acts on the

trated urine.

tubular fluid passes through these ducts, thereby con-

the presence of ADH, the permeability of the collect-

causing extreme dilution of the urine. Conversely, in

fore allows extreme loss of water into the urine, also

and ducts become almost impermeable to water, which

Briefly, in the absence of ADH, the collecting tubules

excretion of water by the kidneys (antidiuresis). This

The injection of extremely minute quantities of

Physiological Functions of ADH

functional similarities.

The similarity of the molecules explains their partial

replace isoleucine and leucine of the oxytocin molecule.

except that in vasopressin, phenylalanine and arginine

Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH

Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-

tides, each containing nine amino acids. Their amino

Both oxytocin and ADH (vasopressin) are polypep-

Chemical Structures of ADH

terminals.

hormone separates almost immediately. The neuro-

because they are only loosely bound to each other, the

physin and the hormone are secreted together, but

absorbed into adjacent capillaries. Both the neuro-

cular nuclei, the hormone is immediately released

When nerve impulses are transmitted downward

its primary hormone.

whereas oxytocin is formed primarily in the paraven-

posterior pituitary gland, requiring several days to

transported in combination with “carrier” proteins

rior pituitary. The reason for this is that the hormones

after a transient decrease for a few days; they are then

pituitary hormones continue to be secreted normally,

but the entire hypothalamus is left intact, the posterior

928

Unit XIV

Endocrinology and Reproduction

If the pituitary stalk is cut above the pituitary gland

secreted by the cut ends of the fibers within the hypo-
thalamus and not by the nerve endings in the poste-

are initially synthesized in the cell bodies of the
supraoptic and paraventricular nuclei and are then

called neurophysins down to the nerve endings in the

reach the gland.

ADH is formed primarily in the supraoptic nuclei,

tricular nuclei. Each of these nuclei can synthesize
about one sixth as much of the second hormone as of

along the fibers from the supraoptic or paraventri-

from the secretory granules in the nerve endings by
the usual secretory mechanism of exocytosis and is

physin has no known function after leaving the nerve

and Oxytocin

acid sequences are the following:

GlyNH

Note that these two hormones are almost identical

ADH—as small as 2 nanograms—can cause decreased

antidiuretic effect is discussed in detail in Chapter 28.

prevents significant reabsorption of water and there-

ing ducts and tubules to water increases greatly and
allows most of the water to be reabsorbed as the

serving water in the body and producing very concen-

collecting ducts to increase their permeability is only

branes of the tubular epithelial cells of the collecting

immediately inside the cell membrane are a large

permeable pores called

which then causes the vesicles to insert into the apical

process temporarily provides many new pores that
allow free diffusion of water from the tubular fluid
through the tubular epithelial cells and into the renal

Chapter 28 in relation to the urine-concentrating

Osmotic Regulation.

solution is injected into the artery that supplies the

paraventricular nuclei immediately transmit impulses
into the posterior pituitary to release large quantities

artery causes cessation of the impulses and therefore

Optic chiasm

Hypothalamic-
hypophysial
tract

Supraoptic
nucleus

Anterior pituitary

Posterior pituitary

Mamillary body

Paraventricular

nucleus

Hypothalamic control of the posterior pituitary.

Figure 75–9

ture, function, and regulation. Physiol Rev 81:629, 2001.

Gimpl G, Fahrenholz F: The oxytocin receptor system: struc-

Rev 80:1523, 2000.

structure, function, and regulation of secretion. Physiol

Freeman ME, Kanyicska B, Lerant A, Nagy G: Prolactin:

Metab 84:4379, 1999.

Eugster EA, Pescovitz OH: Gigantism. J Clin Endocrinol

insulin-like growth factor systems. Endocr Rev 24:737,

dermal homeostasis: the role of the growth hormone and

Edmondson SR,Thumiger SP, Werther GA,Wraight CJ: Epi-

interactions during stress. Ann N Y Acad Sci 1018:25, 2004.

Dunn AJ, Swiergiel AH, Palamarchouk V: Brain circuits

treatment. Lancet 363:1977, 2004.

related disorders: insights into causation, diagnosis, and

Dattani M, Preece M: Growth hormone deficiency and

adults. Annu Rev Med 54:513, 2003.

Cummings DE, Merriam GR: Growth hormone therapy in

63:141, 2001.

have related and independent roles. Annu Rev Physiol

axis: growth hormone and the insulin-like growth factors

Butler AA, Le Roith D: Control of growth by the somatropic

neurohypophysial system. Physiol Rev 81:1197, 2001.

Burbach JP, Luckman SM, Murphy D, Gainer H: Gene

Science Limited, 2002.

Endocrinology, 3rd ed. Philadelphia: Mosby, Elsevier

Besser GM,

Thorner MO:

Comprehensive Clinical

84:169, 2004.

roendocrine control of body fluid metabolism. Physiol Rev

Antunes-Rodrigues J, de Castro M, Elias LL, et al: Neu-

milk letdown

ning of suckling, milk begins to flow. This mechanism

mammary glands. In less than a minute after the begin-

carried by the blood to the breasts, where it causes

by the posterior pituitary gland. The oxytocin is then

in the hypothalamus, which causes release of oxytocin

This mechanism works as follows: The suckling stim-

can obtain it by suckling.

In lactation, oxytocin causes milk to be expressed from

that is far better understood than its role in delivery.

cause increased secretion of oxytocin. These effects

during labor, especially during the last stage. (3) Stim-

(2) The amount of oxytocin in the plasma increases

indicating a possible effect of oxytocin during delivery.

sectomized animal, the duration of labor is prolonged,

is supported by the following facts: (1) In a hypophy-

partially responsible for causing birth of the baby. This

especially toward the end of gestation. Therefore,

erfully stimulates contraction of the pregnant uterus,

in accordance with its name, pow-

oxytocin,

The

pressure feedback mechanism, refer to Chapter 28.

secretion. For further details about this blood volume-

aortic, and pulmonary regions also stimulates ADH

site occurs, with greatly increased ADH secretion.

tors are unexcited as a result of underfilling, the oppo-

to inhibit ADH secretion. Conversely, when the recep-

overfilling. When excited, they send signals to the brain

The atria have stretch receptors that are excited by

following.

to as high as 50 times normal. The cause of this is the

cent or more; the secretory rate then sometimes rises

tion is decreased blood volume. This occurs especially

One of the stimuli for causing intense ADH secre-

ADH has another name,

fore increasing the arterial pressure. For this reason,

concentrations of ADH have a potent effect of con-

increased water conservation by the kidneys, higher

Whereas minute concentrations of ADH cause

Blood Volume

and Increased ADH Secretion Caused by Low

Vasoconstrictor and Pressor Effects of ADH,

Further details on the role of ADH in controlling

body fluids.

body fluids inhibit them. A feedback control system is

fluids stimulate the supraoptic nuclei, whereas dilute

Regardless of the mechanism, concentrated body

anteroventral wall of the third ventricle.

nuclei), others believe that they are located in the

decreases the signal for ADH secretion. Although

osmosis in the opposite direction, into the cell, and this

extracellular fluid becomes too dilute, water moves by

cause additional ADH secretion. Conversely, when the

ceptor cell,

decreasing its size and initiating

trated, fluid is pulled by osmosis out of the osmore-

When the extracellular fluid becomes too concen-

osmoreceptors.

clear. Yet somewhere in or near the hypothalamus

the extracellular fluid controls ADH secretion is not

The precise way that the osmotic concentration of

Pituitary Hormones and Their Control by the Hypothalamus

Chapter 75

929

are modified neuron receptors called

appropriate nerve signals in the hypothalamus to

some researchers place these osmoreceptors in the
hypothalamus itself (possibly even in the supraoptic

organum vasculosum, a highly vascular structure in the

available to control the total osmotic pressure of the

renal function and body fluid osmolality are presented
in Chapter 28.

stricting the arterioles throughout the body and there-

vasopressin.

strongly when the blood volume decreases 15 to 25 per

Decreased stretch of the baroreceptors of the carotid,

Oxytocic Hormone

Oxytocin Causes Contraction of the Pregnant Uterus.

hormone

many obstetricians believe that this hormone is at least

ulation of the cervix in a pregnant animal elicits
nervous signals that pass to the hypothalamus and

and this possible mechanism for aiding in the birth
process are discussed in much more detail in Chapter
82.

Oxytocin Aids in Milk Ejection by the Breasts.

Oxytocin also

plays an especially important role in lactation—a role

the alveoli into the ducts of the breast so that the baby

ulus on the nipple of the breast causes signals to be
transmitted through sensory nerves to the oxytocin
neurons in the paraventricular and supraoptic nuclei

contraction of myoepithelial cells that lie outside of
and form a latticework surrounding the alveoli of the

is called

or milk ejection. It is discussed

further in Chapter 82 in relation to the physiology of
lactation.

References

regulation in the magnocellular hypothalamo-

involved in corticotropin-releasing factor–norepinephrine

2003.

Behav 77:731, 2002.

thirst: similarities and dissimilarities in signals. Physiol

Stricker EM, Sved AF: Controls of vasopressin secretion and

Curr Opin Pharmacol 3:672, 2003.

Paisley AN, Trainer PJ: Medical treatment in acromegaly.

kidney: from molecules to medicine. Physiol Rev 82:205,

Nielsen S, Frokiaer J, Marples D, et al: Aquaporins in the

understanding. Curr Opin Pharmacol 3:642, 2003.

Murray RD: Adult growth hormone replacement: current

1007:143, 2003.

Steroid regulation of GnRH neurons. Ann N Y Acad Sci

Moenter SM, Defazio RA, Straume M, Nunemaker CS:

Longo VD, Finch CE: Evolutionary medicine: from dwarf

Regul Integr Comp Physiol 285:R715, 2003.

Lohmeier TE: Neurohypophysial hormones. Am J Physiol

phia: WB Saunders, 2003.

Williams Textbook of Endocrinology, 10th ed. Philadel-

Larsen PR, Kronenberg HM, Melmed S, Polonsky KS:

prime time? Ann Intern Med 137:190, 2002.

Isley WL: Growth hormone therapy for adults: not ready for

N Y Acad Sci 1019:294, 2004.

function in mechanosensitive growth factor signaling. Ann

Goldspink G: Age-related muscle loss and progressive dys-

930

Unit XIV

Endocrinology and Reproduction

model systems to healthy centenarians? Science 299:1342,
2003.

2002.