Endocrine Anatomy and Physiology

The endocrine system has far-reaching effects

in the human body because of its links with the
nervous system and the immune system. The
hormones secreted by the endocrine system are
affected in large part by structures in the central
nervous system, such as the hypothalamus.
Other structures located in the brain, such as
the pituitary gland, are endocrine glands that
influence the function of a large number of other
endocrine glands. The effects of hormones
secreted by the endocrine system affect the
nervous system and are, in turn, mediated by
the nervous system. The adrenal medulla, for
example, secretes a number of substances (eg,
norepinephrine and epinephrine) that act as
neurotransmitters. The immune system also
interacts closely with the endocrine system. It
responds to the introduction of foreign agents by means of chemicals (eg, interleukins, interferons) and is
regulated by hormones secreted by the adrenal cortex.

In addition to the hormones secreted by the major endocrine glands, other tissues produce hormones that
are secreted into body fluids and act on nearby cells and tissues. The gastrointestinal mucosa produces
hormones (eg, gastrin, enterogastrone, secretin, and cholecystokinin) that are important in the digestive
process. The kidneys produce erythropoietin, a hormone that stimulates the bone marrow to produce red
blood cells. The white blood cells produce cytokines that actively participate in inflflammatory and immune
responses. Hormones are important in regulation of the internal environment of the body and affect every
aspect of life. Some hormones target specific tissues; for example, adrenocorticotropic hormone
(ACTH), or corticotrophin, is secreted by the anterior pituitary gland and targets the adrenal cortex to
increase the secretion of the hormones of the adrenal cortex (ie, glucocorticoids, mineralocorticoids, and
androgens). Other hormones affect a wide variety of cells and tissues of the body. Thyroid hormone is
one example; it affects metabolic activity of cells throughout the body.

GLANDS OF THE ENDOCRINE SYSTEM

The endocrine glands include the
pituitary, thyroid, parathyroids,
adrenals, pancreatic islets, ovaries,
and testes. Endocrine glands
secrete their products directly into
the blood stream, which
differentiates them from exocrine
glands, such as sweat glands,
which secrete their products
through ducts onto epithelial
surfaces or into the gastrointestinal
tract. The hypothalamus is the link
between the nervous system and
the endocrine system.

FUNCTION AND REGULATION OF HORMONES

The chemical substances secreted by the endocrine glands are called hormones. Hormones help to
regulate organ function in concert with the nervous system. This dual regulatory system, in which rapid
action by the nervous system is balanced by slower hormonal action, permits precise control of organ
functions in response to varied changes within and outside the body. The endocrine glands are composed
of secretory cells arranged in minute clusters known as acini. No ducts are present, but the glands have a
rich blood supply so that the hormones they produce enter the bloodstream rapidly. In the healthy
physiologic state, hormone concentration in the bloodstream is maintained at a relatively constant level.
When the hormone concentration rises, further production of that hormone is inhibited. When the
hormone concentration falls, the rate of production of that hormone increases. This mechanism for
regulating hormone concentration in the bloodstream is called negative feedback, which is important in
the regulation of many biologic processes.

Major Actions and Sources of selected Hormones

CLASSIFICATION AND ACTION OF HORMONES

Hormones are classified as steroid hormones (such as hydrocortisone), peptide or protein

hormones (such as insulin), and amine hormones (such as epinephrine). These different classes of
hormones act on the target tissues by different mechanisms. Hormones can alter the function of the target
tissue by interacting with chemical receptors located either on the cell membrane or in the interior of the
cell. Peptide and protein hormones interact with receptor sites on the cell surface, which results in the
stimulation of the intracellular enzyme adenyl cyclase. This results in increased production of cyclic 3′, 5′-
adenosine monophosphate (cyclic AMP). The cyclic AMP inside the cell alters enzyme activity. Thus,
cyclic AMP is the “second messenger” that links the peptide hormone at the cell surface to a change in
the intracellular environment. Some of the protein and peptide hormones may also act by changing
membrane permeability. These hormones act within seconds or minutes. The mechanism of action for
amine hormones is similar to that for peptide hormones. Steroid hormones, because of their smaller size
and higher lipid solubility, penetrate the cell membranes and interact with intracellular receptors. This
steroid–receptor complex modifies cell metabolism and formation of messenger ribonucleic acid (RNA)
from deoxyribonucleic acid (DNA). The messenger RNA then stimulates protein synthesis within the cell.
Steroid hormones require several hours to exert their effects because they exert their action by the
modification of protein synthesis.

PITUITARY FUNCTION
Commonly referred to as the master gland, the pituitary
secretes hormones that control the secretion of
hormones by other endocrine glands. The pituitary itself is
controlled by the hypothalamus, an adjacent area of the brain
connected to the pituitary by the pituitary stalk.

Posterior Pituitary
The important hormones secreted by the posterior lobe of
the pituitary gland are vasopressin (antidiuretic
hormone [ADH]) and oxytocin. These hormones are
synthesized in the hypothalamus and travel from the
hypothalamus to the posterior pituitary gland for storage. Vasopressin controls the excretion of water by
the
kidney; its secretion is stimulated by an increase in the osmolality of the blood or by a decrease in blood
pressure. Oxytocin facilitates milk ejection during lactation and increases the force of uterine contractions
during labor and delivery. Oxytocin secretion is stimulated during pregnancy and at childbirth.

Anterior Pituitary
The major hormones of the anterior pituitary gland are follicle stimulating hormone (FSH), luteinizing
hormone (LH), prolactin, ACTH, thyroid-stimulating hormone (TSH), and growth hormone (also referred to
as somatotropin). The secretion of these major hormones is controlled by releasing factors secreted by
the hypothalamus. These releasing factors reach the anterior pituitary by way of the bloodstream in a
special circulation called the pituitary portal blood system. Other hormones include melanocyte-
stimulating hormone and beta-lipotropin; the function of lipotropin is poorly understood. The hormones
released by the anterior pituitary enter the general circulation and are transported to their target organs.
The main function of TSH, ACTH, FSH, and LH is the release of hormones from other endocrine glands.
Prolactin acts on the breast to stimulate milk production. Growth hormone has wide spread effects on
many target tissues and is discussed later. Hormones that stimulate other organs and tissues are
discussed in conjunction with their target organs. Growth hormone is a protein hormone that increases
protein synthesis in many tissues, increases the breakdown of fatty acids in adipose tissue, and increases
the glucose level in the blood. These actions of growth hormone are essential for normal growth, although
other hormones, such as thyroid hormone and insulin, are required as well. Stress, exercise, and low
blood glucose levels increase the secretion of growth hormone. The halflife of growth hormone activity in
the blood is 20 to 30 minutes; the hormone is largely inactivated in the liver.

Thyroid Function

It consists of two lateral lobes connected by an isthmus. The gland is about 5 cm long and 3 cm wide and
weighs about 30 g. The blood flow to the thyroid is very high (about 5 mL/min per gram of thyroid tissue),
about five times the blood flow to the liver. This reflects the high metabolic activity of the thyroid gland.
The thyroid gland produces three hormones: thyroxine (T4), triiodothyronine (T3), and calcitonin.
Thyroxine and triiodothyronine are referred to collectively as thyroid hormone.

Thyroid Hormone
The two separate hormones, thyroxine (T4) and triiodothyronine (T3), that are produced by the thyroid
gland and that make up thyroid hormone, are amino acids that have the unique property of containing
iodine molecules bound to the amino acid structure. T4 contains four iodine atoms in each molecule, and
T3 contains only three. These hormones are synthesized and stored bound to proteins in the cells of the
thyroid gland until needed for release into the bloodstream. About 75% of bound thyroid hormone is
bound to thyroxine-binding globulin (TBG); the remaining bound thyroid hormone is bound to thyroid-
binding prealbumin and albumin.

ROLE OF IODINE
Iodine is essential to the thyroid gland for synthesis of its hormones. In fact, the major use of iodine in the
body is by the thyroid, and the major derangement in iodine deficiency is alteration of thyroid function.
Iodide is ingested in the diet and absorbed into the blood in the gastrointestinal tract. The thyroid gland is
extremely efficient in taking up iodide from the blood and concentrating it within the cells, where iodide
ions are converted to iodine molecules, which react with tyrosine (an amino acid) to form the thyroid
hormones.

REGULATION OF THYROID HORMONE

The secretion of T3 and T4 by the thyroid gland is controlled by thyroid-stimulating hormone (TSH, or
thyrotropin) from the anterior pituitary gland. TSH controls the rate of thyroid hormone release. In turn, the
level of thyroid hormone in the blood determines the release of TSH. If thyroid hormone concentration in
the blood decreases, the release of TSH increases, which causes increased output of T3 and T4. This is
an example of negative feedback. Thyrotropin-releasing hormone (TRH), secreted by the hypothalamus,
exerts a modulating influence on the release of TSH from the pituitary. Environmental factors, such as a
decrease in temperature, may lead to increased secretion of TRH, resulting in elevated secretion of
thyroid hormones.

FUNCTION OF THYROXINE AND TRIIODOTHYRONINE

The primary function of the thyroid hormone is to control the cellular metabolic activity. T4, a relatively
weak hormone, maintains body metabolism in a steady state. T3 is about five times as potent as T4 and
has a more rapid metabolic action. These hormones accelerate metabolic processes by increasing the
level of specific enzymes that contribute to oxygen consumption and altering the responsiveness of
tissues to other hormones. The thyroid hormones influence cell replication and are important in brain
development. Thyroid hormone is also necessary for normal growth. The thyroid hormones, through their
widespread effects on cellular metabolism, influence every major organ system.

Calcitonin
Calcitonin, or thyrocalcitonin, is another important hormone secreted by the thyroid gland. It is secreted
in response to high plasma levels of calcium, and it reduces the plasma level of calcium by increasing its
deposition in bone.
PARATHYROID FUNCTION
Parathormone, the protein hormone from the
parathyroid glands, regulates calcium and
phosphorus metabolism. Increased secretion of
parathormone results in increased calcium absorption
from the kidney, intestine, and bones, thereby raising the
blood calcium level. Some actions of this hormone
are increased by the presence of vitamin D.
Parathormone also tends to lower the blood
phosphorus level. Excess parathormone can result in
markedly elevated levels of serum calcium, a potentially
life-threatening situation. When the
product of serum calcium and serum phosphorus (calcium × phosphorus) rises, calcium phosphate may
precipitate in various organs of the body and cause tissue calcification. The serum level of ionized
calcium regulates the output of parathormone. Increased serum calcium results in decreased
parathormone secretion, creating a negative feedback system.

ADRENAL FUNCTION
There are two adrenal glands in the human, each
attached to the upper portion of a kidney. Each
adrenal gland is, in reality, two endocrine glands
with separate, independent functions. The adrenal
medulla at the center of the gland secretes
catecholamines, and the outer portion of the gland,
the adrenal cortex, secretes steroid hormones. The
secretion of hormones from the adrenal cortex is
regulated by the hypothalamicpituitary-adrenal axis. The hypothalamus secretes corticotropin releasing
hormone (CRH), which in turn stimulates the pituitary gland to secrete ACTH. ACTH then stimulates the
adrenal cortex to secrete glucocorticoid hormone (cortisol). Increased levels of the adrenal hormone then
inhibit the production or secretion of CRH and ACTH. This system is an example of a negative feedback
mechanism.

Adrenal Medulla
The adrenal medulla functions as part of the autonomic nervous system. Stimulation of preganglionic
sympathetic nerve fibers, which travel directly to the cells of the adrenal medulla, causes release of the
catecholamine hormones epinephrine and norepinephrine. About 90% of the secretion of the human
adrenal medulla is epinephrine (also called adrenaline). Catecholamines regulate metabolic pathways to
promote catabolism of stored fuels to meet caloric needs from endogenous sources. The major
effects of epinephrine release are to prepare to meet a challenge (fight-or-flight response). Secretion of
epinephrine causes decreased blood flow to tissues that are not needed in emergency situations, such as
the gastrointestinal tract, and causes increased blood flow to tissues that are important for effective fight
or flight, such as cardiac and skeletal muscle. Catecholamines also induce the release of free fatty acids,
increase the basal metabolic rate, and elevate the blood glucose level.

Adrenal Cortex
A functioning adrenal cortex is necessary for life; adrenocortical secretions make it possible for the body
to adapt to stress of all kinds. The three types of steroid hormones produced by the adrenal cortex are
glucocorticoids, the prototype of which is hydrocortisone; mineralocorticoids, mainly aldosterone; and
sex hormones, mainly androgens (male sex hormones). Without the adrenal cortex, severe stress would
cause peripheral circulatory failure, circulatory shock, and prostration. Survival in the absence of a
functioning adrenal cortex is possible only with nutritional, electrolyte, and fluid replacement and
appropriate replacement with exogenous adrenocortical hormones.

GLUCOCORTICOIDS
The glucocorticoids are so named because they have an important influence on glucose metabolism:
increased hydrocortisone secretion results in elevated blood glucose levels. However, the glucocorticoids
have major effects on the metabolism of almost all organs of the body. Glucocorticoids are secreted from
the adrenal cortex in response to the release of ACTH from the anterior lobe of the pituitary gland. This
system represents an example of negative feedback. The presence of glucocorticoids in the blood inhibits
the release of corticotropin-releasing factor from the hypothalamus and also inhibits ACTH secretion from
the pituitary. The resultant
decrease in ACTH secretion causes diminished release of glucocorticoids from the adrenal cortex.
Glucocorticoids (in the form of corticosteroids) are administered frequently to inhibit the inflammatory
response to tissue injury and suppress allergic manifestations. Their side effects include the development
of diabetes mellitus, osteoporosis, peptic ulcer, increased protein breakdown resulting in muscle wasting
and poor wound healing, and redistribution of body fat. Large amounts of exogenously administered
glucocorticoids in the blood inhibit the release of ACTH and endogenous glucocorticoids. Because of this,
the adrenal cortex can atrophy. If exogenous glucocorticoid administration is discontinued suddenly,
adrenal insufficiency results because of the inability of the atrophied cortex to respond adequately.

MINERALOCORTICOIDS
Mineralocorticoids exert their major effects on electrolyte metabolism. They act principally on the renal
tubular and gastrointestinal epithelium to cause increased sodium ion absorption in exchange for
excretion of potassium or hydrogen ions. ACTH only minimally influences aldosterone secretion. It is
primarily secreted in response to the presence of angiotensin II in the bloodstream. Angiotensin II is a
substance that elevates the
blood pressure by constricting arterioles. Its concentration is increased when renin is released from the
kidney in response to decreased perfusion pressure. The resultant increased aldosterone levels promote
sodium reabsorption by the kidney and the gastrointestinal tract, which tends to restore blood pressure to
normal. The release of aldosterone is also increased by hyperkalemia. Aldosterone is the primary
hormone for the long-term regulation of sodium balance.

ADRENAL SEX HORMONES (ANDROGENS)

Androgens, the third major type of steroid hormones produced by the adrenal cortex, exert effects similar
to those of male sex hormones. The adrenal gland may also secrete small amounts of some estrogens, or
female sex hormones. ACTH controls the secretion of adrenal androgens. When secreted in normal
amounts, the adrenal androgens probably have little effect, but when secreted in excess, in certain inborn
enzyme deficiencies, masculinization may result. This is termed the adrenogenital syndrome.

THE PANCREAS
The pancreas, located in the upper abdomen, has endocrine as well as exocrine functions. The
secretion of pancreatic enzymes into the gastrointestinal tract through the pancreatic duct represents its
exocrine function. The secretion of insulin, glucagon, and somatostatin directly into the bloodstream
represents its endocrine function.

Exocrine Pancreas
The secretions of the exocrine portion of the pancreas are collected in the pancreatic duct, which joins the
common bile duct and enters the duodenum at the ampulla of Vater. Surrounding the ampulla is the
sphincter of Oddi, which partially controls the rate at which secretions from the pancreas and the
gallbladder enter the duodenum.
The secretions of the exocrine pancreas are digestive enzymes high in protein content and an electrolyte-
rich fluid. The secretions are very alkaline because of their high concentration of sodium bicarbonate and
are capable of neutralizing the highly acid gastric juice that enters the duodenum. The enzyme secretions
include amylase, which aids in the digestion of carbohydrates; trypsin, which aids in the digestion of
proteins; and lipase, which aids in the digestion of fats. Other enzymes that promote the breakdown of
more complex foodstuffs are also secreted.

Hormones originating in the gastrointestinal tract stimulate the secretion of these exocrine pancreatic
juices. Secretin is the major stimulus for increased bicarbonate secretion from the pancreas, and the
major stimulus for digestive enzyme secretion is the hormone CCK-PZ. The vagus nerve also influences
exocrine pancreatic secretion.

Endocrine Pancreas
The islets of Langerhans, the endocrine part of the pancreas, are collections of cells embedded in the
pancreatic tissue. They are composed of alpha, beta, and delta cells. The hormone produced by the beta
cells is called insulin; the alpha cells secrete glucagon and the delta cells secrete somatostatin.

INSULIN
A major action of insulin is to lower blood glucose by permitting entry of the glucose into the cells of the
liver, muscle, and other tissues, where it is either stored as glycogen or used for energy. Insulin also
promotes the storage of fat in adipose tissue and the synthesis of proteins in various body tissues. In the
absence of insulin, glucose cannot enter the cells and is excreted in the urine. This condition, called
diabetes mellitus, can be diagnosed by high levels of glucose in the blood. In diabetes mellitus, stored
fats and protein are used for energy instead of glucose, with consequent loss of body mass. The level of
glucose in the blood normally regulates the rate of insulin secretion from the pancreas.

GLUCAGON
The effect of glucagon (opposite to that of insulin) is chiefly to raise the blood glucose by converting
glycogen to glucose in the liver. Glucagon is secreted by the pancreas in response to a decrease in the
level of blood glucose.

SOMATOSTATIN
Somatostatin exerts a hypoglycemic effect by interfering with release of growth hormone from the pituitary
and glucagon from the pancreas, both of which tend to raise blood glucose levels.