Lec 3&4 Endocrinology Dr.Noori. M.

Luaibi

Pituitary Hormones and Their Control by the Hypothalamus

Pituitary Gland and Its Relation to the Hypothalamus Pituitary Gland:

Two Distinct Parts–The Anterior and Posterior Lobes.

The pituitary gland (Figure 75–1), also called the hypophysis, is a

small gland—about 1 centimeter in diameter and 0.5 to 1 gram in weight
that lies in the sella turcica, a bony cavity at the base of the brain, and is
connected to the hypothalamus by the pituitary (or hypophysial) stalk.
Physiologically, the pituitary gland is divisible into two distinct portions: the
anterior pituitary, also known as the adenohypophysis, and the posterior
pituitary, also known as the neurohypophysis. Between these is a small,
relatively avascular zone called the pars intermedia, which is almost absent
in the human being but is much larger and much more functional in some
lower animals.

Embryologically, the two portions of the pituitary originate from

different sources—the anterior pituitary from Rathke’s pouch, which is an
embryonic invagination of the pharyngeal epithelium, and the posterior
pituitary from a neural tissue outgrowth from the hypothalamus.The origin
of the anterior pituitary from the pharyngeal epithelium explains the
epithelioid nature of its cells, and the origin of the posterior pituitary from
neural tissue explains the presence of large numbers of glial-type cells in this
gland.

Six important peptide hormones plus several less important ones are
secreted by the anterior pituitary, and two important peptide hormones are
secreted by the posterior pituitary.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

The hormones of the anterior pituitary play major roles in the control
of metabolic functions throughout the body, (Figure 75–2),

1. Growth hormone promotes growth of the entire body by affecting

protein formation, cell multiplication, and cell differentiation.
2. Adrenocorticotropin (corticotropin) controls the secretion of some of
the adrenocortical hormones, which affect the metabolism of glucose,
proteins, and fats.
3. Thyroid-stimulating hormone (thyrotropin) controls the rate of
secretion of thyroxine and triiodothyronine by the thyroid gland, and
these hormones control the rates of most intracellular chemical
reactions in the body.
4. Prolactin promotes mammary gland development and milk
production.
5. Two separate gonadotropic hormones, follicle-stimulating hormone
and luteinizing hormone, control growth of the ovaries and testes, as
well as their hormonal and reproductive activities.

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

1. Antidiuretic hormone (also called vasopressin) controls the rate of

water excretion into the urine, thus helping to control the
concentration of water in the body fluids.
2. 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.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Anterior Pituitary Gland Contains Several Different Cell Types That

Synthesize and Secrete Hormones.

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

theanterior pituitary gland.With special stains attached to high-affinity

antibodies that bind with the distinctive hormones, at least five cell types can

be differentiated provides (Figure 75–3) a summary of these cell types, the

hormones they produce, and their physiological actions. These five cell

types are:

1. Somatotropes—human growth hormone (hGH)

2. Corticotropes—adrenocorticotropin (ACTH)

3. Thyrotropes—thyroid-stimulating hormone (TSH)

4. Gonadotropes—gonadotropic hormones, which include both luteinizing

hormone (LH) and folliclestimulating hormone (FSH)

5. Lactotropes—prolactin (PRL)

About 30 to 40 per cent of the anterior pituitary cells are somatotropes

that secrete growth hormone, and about 20 per cent are corticotropes that
secrete ACTH.

Each of the other cell types accounts for only 3 to 5 per cent of the
total; nevertheless, they secrete powerful hormones for controlling thyroid
function, sexual functions, and milk secretion by the breasts.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Somatotropes stain strongly with acid dyes and are therefore called
acidophils. Thus, pituitary tumors that secrete large quantities of human
growth hormone are called acidophilic tumors.

Posterior Pituitary Hormones Are Synthesized by Cell Bodies in the

Hypothalamus.

The bodies of the cells that secrete the posterior pituitary hormones
are not located in the pituitary gland itself but are large neurons, called
magnocellular neurons, located in the supraoptic and paraventricular nuclei
of the hypothalamus. The hormones are then transported in the axoplasm of
the neurons’ nerve fibers passing from the hypothalamus to the posterior
pituitary gland.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Hypothalamus Controls Pituitary Secretion

Almost all secretion by the pituitary is controlled by either hormonal
or nervous signals from the hypothalamus. Indeed, when the pituitary gland
is removed from its normal position beneath the hypothalamus and
transplanted to some other part of the body, its rates of secretion of the
different hormones (except for prolactin) fall to very low levels.

Secretion from the posterior pituitary is controlled by nerve signals

that originate in the hypothalamus and terminate in the posterior pituitary. In
contrast, secretion by the anterior pituitary is controlled by hormones called
hypothalamic releasing and hypothalamic inhibitory hormones (or factors)
secreted within the hypothalamus itself and then conducted, , (Figure 75–4),
to the anterior pituitary through minute blood vessels called hypothalamic-
hypophysial portal vessels. In the anterior pituitary, these releasing and
inhibitory hormones act on the glandular cells to control their secretion.

The hypothalamus receives signals from many sources in the nervous

system. Thus, when a person is exposed to pain, a portion of the pain signal
is transmitted into the hypothalamus. Likewise, when a person experiences
some powerful depressing or exciting thought, a portion of the signal is
transmitted into the hypothalamus. Olfactory stimuli denoting pleasant or
unpleasant smells transmit strong signal components directly and through
the amygdaloid nuclei into the hypothalamus. Even the concentrations of
nutrients, electrolytes, water, and various hormones in the blood excite or
inhibit various portions of the hypothalamus. Thus, the hypothalamus is a
collecting center for information concerning the internal well-being of the
body, and much of this information is used to control secretions of the many
globally important pituitary hormones.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Hypothalamic-Hypophysial Portal Blood Vessels of the Anterior

Pituitary Gland

The anterior pituitary is a highly vascular gland with extensive

capillary sinuses among the glandular cells. Almost all the blood that enters
these sinuses passes first through another capillary bed in the lower
hypothalamus. The blood then flows through small hypothalamic-
hypophysial portal blood vessels into the anterior pituitary sinuses.

(Figure 75–4) shows the lowermost portion of the hypothalamus,

called the median eminence, which connects inferiorly with the pituitary
stalk. Small arteries penetrate into the substance of the median eminence and
then additional small vessels return to its surface, coalescing to form the
hypothalamic-hypophysial portal blood vessels. These pass downward along
the pituitary stalk to supply blood to the anterior pituitary sinuses.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Hypothalamic Releasing and Inhibitory Hormones Are Secreted into

the Median Eminence.

Special neurons in the hypothalamus synthesize and secrete the

hypothalamic releasing and inhibitory hormones that control secretion of the
anterior pituitary hormones.These neurons 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.

The endings of these fibers are different from most endings in the
central nervous system, in that their function is not to transmit signals from
one neuron to another but rather to secrete the hypothalamic releasing and
inhibitory hormones into the tissue fluids.

These hormones are immediately absorbed into the hypothalamic-

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

Hypothalamic Releasing and Inhibitory Hormones Control Anterior

Pituitary Secretion.

The function of the releasing and inhibitory hormones is to control

secretion of the anterior pituitary hormones. For most of the anterior
pituitary hormones, it is the releasing hormones that are important, but for
prolactin, a hypothalamic inhibitory hormone probably exerts more control.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

The major hypothalamic releasing and inhibitory hormones are the

following:

1. Thyrotropin-releasing hormone (TRH), whichcauses release of thyroid-

stimulating hormone

2. Corticotropin-releasing hormone (CRH), which causes release of

adrenocorticotropin

3. Growth hormone–releasing hormone (GHRH), which causes release of

growth hormone, and growth hormone inhibitory hormone (GHIH), also
called somatostatin, which inhibits release of growth hormone

4. Gonadotropin-releasing hormone (GnRH), which causes release of the

two gonadotropic hormones, luteinizing hormone and follicle-stimulating
hormone

5. Prolactin inhibitory hormone (PIH), which causes inhibition of prolactin

secretion

There are some additional hypothalamic hormones, including one that

stimulates prolactin secretion and perhaps others that inhibit release of the
anterior pituitary hormones. Each of the more important hypothalamic
hormones is discussed in detail as the specific hormonal systems controlled
by them are presented in this and subsequent chapters.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Physiological Functions of Growth Hormone

1. Growth Hormone Promotes Growth of Many Body Tissues

2. Growth Hormone Has Several Metabolic Effects
3. Growth Hormone Promotes Protein Deposition in Tissues
4. Enhancement of Amino Acid Transport Through the Cell Membranes
5. Enhancement of RNA Translation to Cause Protein Synthesis by the
Ribosomes.
6. Increased Nuclear Transcription of DNA to Form RNA.
7. Decreased Catabolism of Protein and Amino Acids.
8. Growth Hormone Enhances Fat Utilization for Energy
9. “Ketogenic” Effect of Growth Hormone.
10.Growth Hormone Decreases Carbohydrate Utilization
11.Necessity of Insulin and Carbohydrate for the Growth- Promoting
Action of Growth Hormone.
12.Growth Hormone Stimulates Cartilage and Bone Growth
13.Growth Hormone Exerts Much of Its Effect Through Intermediate
Substances Called “Somatomedins” (Also Called “Insulin-Like
Growth Factors”)
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Regulation of Growth Hormone Secretion

For many years it was believed that growth hormone was secreted
primarily during the period of growth but then disappeared from the blood at
adolescence. This has proved to be untrue. After adolescence, secretion
decreases slowly with aging, finally falling to about 25 per cent of the
adolescent level in very old age.

Growth hormone is secreted in a pulsatile pattern, increasing and

decreasing. The precise mechanisms that control secretion of growth
hormone are not fully understood, but several factors related to a person’s
state of nutrition or stress are known to stimulate secretion:

(1) starvation, especially with severe protein deficiency;

(2) hypoglycemia or low concentration of fatty acids in the blood;

(3) exercise;

(4) excitement;

(5) trauma.

(6) ghrelin, a hormone secreted by the stomach before meals ,

Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Table 75–3 Factors That Stimulate or Inhibit Secretion of Growth

Hormone

Stimulate Growth Hormone Inhibit Growth Hormone Secretion

1. Decreased blood glucose

2. Decreased blood free fatty acid
3. Starvation or fasting, protein deficiency
4. Trauma, stress, excitement
5. Exercise
6. Testosterone, estrogen
7. Deep sleep ( stages II and IV)
8. Growth hormone–releasing hormone

Inhibit Growth Hormone Secretion Secretion

1. glucose Increased blood glucose

2. Increased blood free fatty acids
3. Aging
4. Obesity
5. Growth hormone inhibitory hormone (somatostatin)
6. Growth hormone (exogenous)
7. Somatomedins (insulin-like growth factors)

Abnormalities of Growth Hormone Secretion

Panhypopituitarism. This term means decreased secretion of all the anterior

pituitary hormones. The decrease in secretion may be congenital (present
from birth), or it may occur suddenly or slowly at any time during life, most
often resulting from a pituitary tumor that destroys the pituitary gland.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Dwarfism. Most instances of dwarfism result from generalized

deficiency of anterior pituitary secretion (panhypopituitarism) during
childhood. In general, all the physical parts of the body develop in
appropriate proportion to one another, but the rate of development is greatly
decreased. A child who has reached the age of 10 years may have the bodily
development of a child aged 4 to 5 years, and the same person at age 20
years may have the bodily development of a child aged 7 to 10 years.

A person with panhypopituitary dwarfism does not pass through

puberty and never secretes sufficient quantities of gonadotropic hormones to
develop adult sexual functions. In one third of such dwarfs, however, only
growth hormone is deficient; these persons do mature sexually and
occasionally reproduce. In one type of dwarfism (the African pygmy and the
Lévi-Lorain dwarf), the rate of growth hormone secretion is normal or high,
but there is a hereditary inability to form somatomedin C, which is a key
step for the promotion of growth by growth hormone.

Panhypopituitarism in the Adult. Panhypopituitarism first occurring

in adulthood frequently results from one of three common bnormalities.Two
tumorous conditions, craniopharyngiomas or chromophobe tumors, may
compress the pituitary gland until the functioning anterior pituitary cells are
totally or almost totally destroyed.The third cause is thrombosis of the
pituitary blood vessels. This abnormality occasionally occurs when a new
mother develops circulatory shock after the birth of her baby.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

The general effects of adult panhypopituitarism are

(1) hypothyroidism,

(2) depressed production of glucocorticoids by the adrenal glands, and

(3) suppressed secretion of the gonadotropic hormones so that sexual

functions are lost.

Thus, the picture is that of a lethargic person (from lack of thyroid

hormones) who is gaining weight (because of lack of fat mobilization by
growth, adrenocorticotropic, adrenocortical, and thyroid hormones) and has
lost all sexual functions. Except for the abnormal sexual functions, the
patient can usually be treated satisfactorily by administering adrenocortical
and thyroid hormones.

Gigantism. Occasionally, the acidophilic, growth hormone–producing

cells of the anterior pituitary gland become excessively active, and
sometimes even acidophilic tumors occur in the gland. As a result, large
quantities of growth hormone are produced. All body tissues grow rapidly,
including the bones. If the condition occurs before adolescence, before the
epiphyses of the long bones have become fused with the shafts, height
increases so that the person becomes a giant— up to 8 feet tall.

The giant ordinarily has hyperglycemia, and the beta cells of the islets
of Langerhans in the pancreas are prone to degenerate because they become
overactive owing to the hyperglycemia. Consequently, in about 10per cent
of giants, full-blown diabetes mellitus eventually develops.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

In most giants, panhypopituitarism eventually develops if they remain

untreated, because the gigantism is usually caused by a tumor of the pituitary
gland that grows until the gland itself is destroyed. This eventual general
deficiency of pituitary hormones usually causes death in early adulthood.
However, once gigantism is diagnosed, further effects can often be blocked
by microsurgical removal of the tumor or by irradiation of the pituitary
gland.

Acromegaly. If an acidophilic tumor occurs after adolescence— that

is, after the epiphyses of the long bones have fused with the shafts—the
person cannot grow taller, but the bones can become thicker and the soft
tissues can continue to grow. Enlargement is especially marked in the bones
of the hands and feet and in the membranous bones, including the cranium,
nose, bosses on the forehead, supraorbital ridges, lower jawbone, and
portions of the vertebrae, because their growth does not cease at
adolescence. consequently, the lower jaw protrudes forward, sometimes as
much as half an inch, the forehead slants forward because of excess
development of the supraorbital ridges, the nose increases to as much as
twice normal size, the feet require size 14 or larger shoes, and the fingers
become extremely thickened so that the hands are almost twice normal size.
In addition to these effects, changes in the vertebrae ordinarily cause a
hunched back, which is known clinically as kyphosis. Finally, many soft
tissue organs, such as the tongue, the liver, and especially the kidneys,
become greatly enlarged.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Posterior Pituitary Gland and Its Relation to the Hypothalamus

The posterior pituitary gland, also called the neurohypophysis, is

composed mainly of glial-like cells called pituicytes.The pituicytes do not
secrete hormones; they 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 of the
hypothalamus,(Figure 75-9) These tracts pass to the neurohypophysis
through the pituitary stalk (hypophysial stalk).The nerve endings are
bulbous knobs that contain many secretory granules.These endings lie on the
surfaces of capillaries, where they secrete two posterior pituitary hormones:
(1) antidiuretic hormone (ADH), also called vasopressin, and (2) oxytocin

If the pituitary stalk is cut above the pituitary gland but the entire
hypothalamus is left intact, the posterior pituitary hormones continue to be
secreted normally, after a transient decrease for a few days; they are then
secreted by the cut ends of the fibers within the hypothalamus and not by the
nerve endings in the posterior pituitary. The reason for this is that the
hormones are initially synthesized in the cell bodies of the supraoptic and
paraventricular nuclei and are then transported in combination with “carrier”
proteins called neurophysins down to the nerve endings in the posterior
pituitary gland, requiring several days to reach the gland.

ADH is formed primarily in the supraoptic nuclei, whereas oxytocin is

formed primarily in the paraventricular nuclei. Each of these nuclei can
synthesize about one sixth as much of the second hormone as of its primary
hormone.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

When nerve impulses are transmitted downward along the fibers from
the supraoptic or paraventricular nuclei, the hormone is immediately
released from the secretory granules in the nerve endings by the usual
secretory mechanism of exocytosis and is absorbed into adjacent capillaries.
Both the neurophysin and the hormone are secreted together, but because
they are only loosely bound to each other, the hormone separates almost
immediately. The neurophysin has no known function after leaving the nerve
terminals.

Chemical Structures of ADH and Oxytocin

Both oxytocin and ADH (vasopressin) are polypeptides, each

containing nine amino acids. Their amino acid sequences are the following:

Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg- GlyNH2

Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Note that these two hormones are almost identical except that in
vasopressin, phenylalanine and arginine replace isoleucine and leucine of the
oxytocin molecule. The similarity of the molecules explains their partial
functional similarities.

Physiological Functions of ADH

The injection of extremely minute quantities of ADH—as small as 2

nanograms—can cause decreased excretion of water by the kidneys
(antidiuresis). Briefly, in the absence of ADH, the collecting tubules and
ducts become almost impermeable to water, which prevents significant
reabsorption of water and therefore allows extreme loss of water into the
urine, also causing extreme dilution of the urine. Conversely, in the presence
of ADH, the permeability of the collecting ducts and tubules to water
increases greatly and allows most of the water to be reabsorbed as the
tubular fluid passes through these ducts, thereby conserving water in the
body and producing very concentrated urine.

The precise mechanism by which ADH acts on the collecting ducts to

increase their permeability is only partially known. Without ADH, the
luminal membranes of the tubular epithelial cells of the collecting ducts are
almost impermeable to water. However, immediately inside the cell
membrane are a large number of special vesicles that have highly
waterpermeable pores called aquaporins.

When ADH acts on the cell, it first combines with membrane

receptors that activate adenylyl cyclase and cause the formation of cAMP
inside the tubular cell cytoplasm.This causes phosphorylation of elements in
the special vesicles, which then causes the vesicles to insert into the apical
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

cell membranes, thus providing many areas of high water permeability. All
this occurs within 5 to 10 minutes. Then, in the absence of ADH, the entire
process reverses in another 5 to 10 minutes. Thus, this 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 interstitial
fluid.Water is then absorbed from the collecting tubules and ducts by
osmosis.

Oxytocic Hormone

Oxytocin Causes Contraction of the Pregnant Uterus. The

hormone oxytocin, in accordance with its name, powerfully stimulates
contraction of the pregnant uterus, specially toward the end of gestation.
Therefore, many obstetricians believe that this hormone is at least partially
responsible for causing birth of the baby.

This is supported by the following facts:

1. In a hypophysectomized animal, the duration of labor is prolonged

indicating a possible effect of oxytocin during delivery.
2. The amount of oxytocin in the plasma increases during labor,
especially during the last stage.
3. Stimulation of the cervix in a pregnant animal elicits nervous signals
that pass to the hypothalamus and cause increased secretion of
oxytocin.
Lec 3&4 Endocrinology Dr.Noori. M. Luaibi

Oxytocin Aids in Milk Ejection by the Breasts.

Oxytocin also plays an especially important role in lactation—a role

that is far better understood than its role in delivery. In lactation, oxytocin
causes milk to be expressed from the alveoli into the ducts of the breast so
that the baby can obtain it by suckling.

This mechanism works as follows:The suckling stimulus on the nipple

of the breast causes signals to be transmitted through sensory nerves to the
oxytocin neurons in the paraventricular and supraoptic nuclei in the
hypothalamus, which causes release of oxytocin by the posterior pituitary
gland. The oxytocin is then carried by the blood to the breasts, where it
causes contraction of myoepithelial cells that lie outside of and form a
latticework surrounding the alveoli of the mammary glands. In less than a
minute after the beginning of suckling, milk begins to flow. This mechanism
is called milk letdown or milk ejection.