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13 Other Endocrine Tissues and Organs, Eicosanoids, and Growth Factors
THE ENDOCRINE SYSTEM
Appearing in the blood in minute quantities, eicosanoids are present only briefly due to rapid inactivation.
To exert their effects, eicosanoids bind to receptors on targetcell plasma membranes and stimulate or inhibit the synthesis of
second messengers such as cyclic AMP. Leukotrienes stimulate
chemotaxis (attraction to a chemical stimulus) of white blood
cells and mediate inflammation. The prostaglandins alter smooth
muscle contraction, glandular secretions, blood flow, reproductive processes, platelet function, respiration, nerve impulse
transmission, lipid metabolism, and immune responses. They
also have roles in promoting inflammation and fever, and in intensifying pain.
C L I NI C AL C ON N E C T ION |
Nonsteroidal Antiinflammatory Drugs
In 1971, scientists solved the long-standing puzzle of how
aspirin works. Aspirin and related nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen (Motrin®), inhibit
cyclooxygenase (COX), a key enzyme involved in prostaglandin synthesis. NSAIDs are used to treat a wide variety of inflammatory disorders, from rheumatoid arthritis to tennis elbow. The success of
NSAIDs in reducing fever, pain, and inflammation shows how prostaglandins contribute to these woes. •
Several of the hormones we have described—insulinlike growth
factor, thymosin, insulin, thyroid hormones, human growth hormone, and prolactin—stimulate cell growth and division. In addition, several more recently discovered hormones called growth
factors play important roles in tissue development, growth, and
repair. Growth factors are mitogenic substances—they cause
growth by stimulating cell division. Many growth factors act
locally, as autocrines or paracrines.
A summary of sources and actions of six important growth
factors is presented in Table 18.12.
26. What hormones are secreted by the gastrointestinal
tract, placenta, kidneys, skin, adipose tissue, and heart?
27. What are some functions of prostaglandins,
leukotrienes, and growth factors?
18.14 The Stress Response
• Describe how the body responds to stress.
It is impossible to remove all of the stress from our everyday
lives. Some stress, called eustress, prepares us to meet certain
challenges and thus is helpful. Other stress, called distress, is
harmful. Any stimulus that produces a stress response is called a
stressor. A stressor may be almost any disturbance of the human
body—heat or cold, environmental poisons, toxins given off by
Summary of Selected Growth Factors
Produced in submaxillary (salivary) glands;
stimulates proliferation of epithelial cells,
fibroblasts, neurons, and astrocytes; suppresses
some cancer cells and secretion of gastric juice
growth factor (PDGF)
Produced in blood platelets; stimulates
proliferation of neuroglia, smooth muscle
fibers, and fibroblasts; appears to have
role in wound healing; may contribute to
Found in pituitary gland and brain; stimulates
proliferation of many cells derived
from embryonic mesoderm (fibroblasts,
adrenocortical cells, smooth muscle fibers,
chondrocytes, and endothelial cells); stimulates
formation of new blood vessels (angiogenesis).
Produced in submandibular (salivary) glands
and hippocampus of brain; stimulates growth
of ganglia in embryo; maintains sympathetic
nervous system; stimulates hypertrophy and
differentiation of neurons.
Produced by normal and tumor cells; stimulate
growth of new capillaries, organ regeneration,
and wound healing.
Produced by various cells as separate
molecules: TGF-alpha has activities similar
to epidermal growth factor; TGF-beta inhibits
proliferation of many cell types.
bacteria, heavy bleeding from a wound or surgery, or a strong
emotional reaction. The responses to stressors may be pleasant or
unpleasant, and they vary among people and even within the same
person at different times.
Your body’s homeostatic mechanisms attempt to counteract
stress. When they are successful, the internal environment remains within normal physiological limits. If stress is extreme,
unusual, or long lasting, the normal mechanisms may not be
enough. In 1936, Hans Selye, a pioneer in stress research, showed
that a variety of stressful conditions or noxious agents elicit a
similar sequence of bodily changes. These changes, called the
stress response or general adaptation syndrome (GAS), are
controlled mainly by the hypothalamus. The stress response occurs in three stages: (1) an initial fight-or-flight response, (2) a
slower resistance reaction, and eventually (3) exhaustion.
The Fight-or-Flight Response
The fight-or-flight response, initiated by nerve impulses from
the hypothalamus to the sympathetic division of the autonomic
nervous system (ANS), including the adrenal medulla, quickly
mobilizes the body’s resources for immediate physical activity
18.14 THE STRESS RESPONSE
(Figure 18.20a). It brings huge amounts of glucose and oxygen to
the organs that are most active in warding off danger: the brain,
which must become highly alert; the skeletal muscles, which may
have to fight off an attacker or flee; and the heart, which must
work vigorously to pump enough blood to the brain and muscles.
During the fight-or-flight response, nonessential body functions
Figure 18.20 Responses to stressors during the stress response. Red arrows (hormonal responses) and green arrows (neural
responses) in (a) indicate immediate fight-or-flight reactions; black arrows in (b) indicate long-term resistance reactions.
Stressors stimulate the hypothalamus to initiate the stress response through the fight-or-flight response and the resistance
CRH = Corticotropin-releasing hormone
ACTH = Adrenocorticotropic hormone
GHRH = Growth hormone–releasing hormone
hGH = Human growth hormone
TRH = Thyrotropin-releasing hormone
TSH = Thyroid-stimulating hormone
in spinal cord
1. Increased heart rate
and force of beat
2. Constriction of blood
vessels of most
viscera and skin
3. Dilation of blood
vessels of heart,
lungs, brain, and
4. Contraction of spleen
5. Conversion of glycogen
into glucose in liver
7. Dilation of airways
8. Decrease in digestive
9. Water retention and
elevated blood pressure
(a) Fight-or-flight responses
Sensitized blood vessels
(b) Resistance reaction
What is the basic difference between the stress response and homeostasis?
(T3 and T4)
of glucose to
C H A P T E R
THE ENDOCRINE SYSTEM
such as digestive, urinary, and reproductive activities are inhibited. Reduction of blood flow to the kidneys promotes release of
renin, which sets into motion the renin–angiotensin–aldosterone
pathway (see Figure 18.16). Aldosterone causes the kidneys to
retain Naϩ, which leads to water retention and elevated blood
pressure. Water retention also helps preserve body fluid volume
in the case of severe bleeding.
The Resistance Reaction
The second stage in the stress response is the resistance reaction
(Figure 18.20b). Unlike the short-lived fight-or-flight response,
which is initiated by nerve impulses from the hypothalamus, the
resistance reaction is initiated in large part by hypothalamic releasing hormones and is a longer-lasting response. The hormones
involved are corticotropin-releasing hormone (CRH), growth hormone–releasing hormone (GHRH), and thyrotropin-releasing
CRH stimulates the anterior pituitary to secrete ACTH, which
in turn stimulates the adrenal cortex to increase release of cortisol. Cortisol then stimulates gluconeogenesis by liver cells,
breakdown of triglycerides into fatty acids (lipolysis), and catabolism of proteins into amino acids. Tissues throughout the
body can use the resulting glucose, fatty acids, and amino acids
to produce ATP or to repair damaged cells. Cortisol also reduces
A second hypothalamic releasing hormone, GHRH, causes
the anterior pituitary to secrete human growth hormone
(hGH). Acting via insulinlike growth factors, hGH stimulates
lipolysis and glycogenolysis, the breakdown of glycogen to
glucose, in the liver. A third hypothalamic releasing hormone,
TRH, stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH). TSH promotes secretion of thyroid
hormones, which stimulate the increased use of glucose for
ATP production. The combined actions of hGH and TSH supply additional ATP for metabolically active cells throughout
The resistance stage helps the body continue fighting a stressor
long after the fight-or-flight response dissipates. This is why your
heart continues to pound for several minutes even after the stressor
is removed. Generally, it is successful in seeing us through a
stressful episode, and our bodies then return to normal. Occasionally, however, the resistance stage fails to combat the stressor, and
the body moves into the state of exhaustion.
The resources of the body may eventually become so depleted
that they cannot sustain the resistance stage, and exhaustion
ensues. Prolonged exposure to high levels of cortisol and other
hormones involved in the resistance reaction causes wasting of
muscle, suppression of the immune system, ulceration of the
gastrointestinal tract, and failure of pancreatic beta cells. In addition, pathological changes may occur because resistance reactions
persist after the stressor has been removed.
Stress and Disease
Although the exact role of stress in human diseases is not known, it
is clear that stress can lead to particular diseases by temporarily
inhibiting certain components of the immune system. Stress-related
disorders include gastritis, ulcerative colitis, irritable bowel syndrome, hypertension, asthma, rheumatoid arthritis (RA), migraine
headaches, anxiety, and depression. People under stress are at a
greater risk of developing chronic disease or dying prematurely.
Interleukin-1, a substance secreted by macrophages of the immune system (see the discussion of ACTH in Section 18.6), is an
important link between stress and immunity. One action of interleukin-1 is to stimulate secretion of ACTH, which in turn stimulates the production of cortisol. Not only does cortisol provide
resistance to stress and inflammation, but it also suppresses further production of interleukin-1. Thus, the immune system turns
on the stress response, and the resulting cortisol then turns off one
immune system mediator. This negative feedback system keeps
the immune response in check once it has accomplished its goal.
Because of this activity, cortisol and other glucocorticoids are
used as immunosuppressive drugs for organ transplant recipients.
CLIN ICA L CON N ECTION |
Posttraumatic stress disorder (PTSD) is an anxiety disorder that may develop in an individual who has experienced,
witnessed, or learned about a physically or psychologically distressing
event. The immediate cause of PTSD appears to be the specific stressors associated with the events. Among the stressors are terrorism,
hostage taking, imprisonment, military duty, serious accidents, torture, sexual or physical abuse, violent crimes, school shootings, massacres, and natural disasters. In the United States, PTSD affects 10%
of females and 5% of males. Symptoms of PTSD include reexperiencing the event through nightmares or flashbacks; avoidance of any
activity, person, place, or event associated with the stressors; loss of
interest and lack of motivation; poor concentration; irritability; and
insomnia. Treatment may include the use of antidepressants, mood
stabilizers, and antianxiety and antipsychotic agents. •
28. What is the central role of the hypothalamus during stress?
29. What body reactions occur during the fight-or-flight
response, the resistance reaction, and exhaustion?
30. What is the relationship between stress and immunity?
18.15 Development of the
• Describe the development of endocrine glands.
The development of the endocrine system is not as localized as
the development of other systems because, as you have already
learned, endocrine organs are distributed throughout the body.
18.15 DEVELOPMENT OF THE ENDOCRINE SYSTEM
About 3 weeks after fertilization, the pituitary gland (hypophysis) begins to develop from two different regions of the ectoderm.
The posterior pituitary (neurohypophysis) is derived from an outgrowth of ectoderm called the neurohypophyseal bud (nooЈ-roˉ-hı¯poˉ-FIZ-e¯-al), located on the floor of the hypothalamus (Figure 18.21).
The infundibulum, also an outgrowth of the neurohypophyseal bud,
connects the posterior pituitary to the hypothalamus. The anterior
pituitary (adenohypophysis) is derived from an outgrowth of ectoderm from the roof of the mouth called the hypophyseal pouch or
Rathke’s pouch. The pouch grows toward the neurohypophyseal
bud and eventually loses its connection with the roof of the mouth.
The thyroid gland develops during the fourth week as a midventral outgrowth of endoderm, called the thyroid diverticulum
(dı¯Ј-ver-TIK-uˉ-lum), from the floor of the pharynx at the level of
the second pair of pharyngeal pouches (Figure 18.21a). The out-
growth projects inferiorly and differentiates into the right and left
lateral lobes and the isthmus of the gland.
The parathyroid glands develop during the fourth week from
endoderm as outgrowths from the third and fourth pharyngeal
pouches (fa-RIN-je¯-al), which help to form structures of the head
The adrenal cortex and adrenal medulla develop during the
fifth week and have completely different embryological origins.
The adrenal cortex is derived from the same region of mesoderm
that produces the gonads. Endocrine tissues that secrete steroid
hormones all are derived from mesoderm. The adrenal medulla is
derived from ectoderm from neural crest cells that migrate to
the superior pole of the kidney. Recall that neural crest cells also
give rise to sympathetic ganglia and other structures of the nervous system (see Figure 14.27b).
Figure 18.21 Development of the endocrine system.
Glands of the endocrine system develop from all three primary germ layers: ectoderm, mesoderm, and endoderm.
C H A P T E R
(a) Location of neurohypophyseal bud, hypophyseal (Rathke’s) pouch,
thyroid diverticulum, and pharyngeal pouches in 28-day embryo
(b) Development of pituitary gland between 5 and 16 weeks
Which endocrine gland develops from tissues with two different embryological origins?
THE ENDOCRINE SYSTEM
The pancreas develops during the fifth through seventh weeks
from two outgrowths of endoderm from the part of the foregut
that later becomes the duodenum (see Figure 29.12c). The two
outgrowths eventually fuse to form the pancreas. The origin of the
ovaries and testes is discussed in Section 28.5.
The pineal gland arises during the seventh week as an outgrowth between the thalamus and colliculi of the midbrain from
ectoderm associated with the diencephalon (see Figure 14.28).
The thymus arises during the fifth week from endoderm of the
third pharyngeal pouches.
31. Compare the origins of the adrenal cortex and adrenal
18.16 Aging and the
• Describe the effects of aging on the endocrine system.
Although some endocrine glands shrink as we get older, their
performance may or may not be compromised. Production of human growth hormone by the anterior pituitary decreases, which
is one cause of muscle atrophy as aging proceeds. The thyroid
gland often decreases its output of thyroid hormones with age,
causing a decrease in metabolic rate, an increase in body fat, and
hypothyroidism, which is seen more often in older people. Because
there is less negative feedback (lower levels of thyroid hormones),
the level of thyroid-stimulating hormone increases with age (see
With aging, the blood level of PTH rises, perhaps due to inadequate dietary intake of calcium. In a study of older women who
took 2400 mg/day of supplemental calcium, blood levels of PTH
were as low as those of younger women. Both calcitriol and calcitonin levels are lower in older persons. Together, the rise in PTH
and the fall in calcitonin level heighten the age-related decrease in
bone mass that leads to osteoporosis and increased risk of fractures (see Figure 18.14).
The adrenal glands contain increasingly more fibrous tissue
and produce less cortisol and aldosterone with advancing age.
However, production of epinephrine and norepinephrine remains
normal. The pancreas releases insulin more slowly with age, and
receptor sensitivity to glucose declines. As a result, blood glucose
levels in older people increase faster and return to normal more
slowly than in younger individuals.
The thymus is largest in infancy. After puberty, its size begins to
decrease, and thymic tissue is replaced by adipose and areolar connective tissue. In older adults, the thymus has atrophied significantly. However, it still produces new T cells for immune responses.
The ovaries decrease in size with age, and they no longer respond
to gonadotropins. The resultant decreased output of estrogens
leads to conditions such as osteoporosis, high blood cholesterol,
and atherosclerosis. FSH and LH levels are high due to less negative feedback inhibition of estrogens. Although testosterone
production by the testes decreases with age, the effects are not
usually apparent until very old age; and many elderly males can
still produce active sperm in normal numbers, even though there
are higher numbers of morphologically abnormal sperm and
decreased sperm motility.
32. Which hormone is related to the muscle atrophy that
occurs with aging?
To appreciate the many ways the endocrine system contributes to
homeostasis of other body systems, examine Focus on Homeostasis: Contributions of the Endocrine System. Next, in Chapter 19,
we will begin to explore the cardiovascular system, starting with
a description of the composition and functions of blood.
D I S O R D E R S : H O M E O S TAT I C I M B A L A N C E S
Disorders of the endocrine system often involve either hyposecretion (hypo- ϭ too little or under), inadequate release of a hormone,
or hypersecretion (hyper- ϭ too much or above), excessive release
of a hormone. In other cases, the problem is faulty hormone receptors, an inadequate number of receptors, or defects in secondmessenger systems. Because hormones are distributed in the blood to
target tissues throughout the body, problems associated with endocrine dysfunction may also be widespread.
Pituitary Gland Disorders
Pituitary Dwarfism, Giantism, and Acromegaly
Several disorders of the anterior pituitary involve human growth
hormone (hGH). Hyposecretion of hGH during the growth years
slows bone growth, and the epiphyseal plates close before normal
height is reached. This condition is called pituitary dwarfism
(see Clinical Connection: Hormonal Abnormalities That Affect
Height in Section 6.5). Other organs of the body also fail to grow,
and the body proportions are childlike. Treatment requires administration of hGH during childhood, before the epiphyseal plates
Hypersecretion of hGH during childhood causes giantism, an
abnormal increase in the length of long bones. The person grows to
be very tall, but body proportions are about normal. Figure 18.22a
shows identical twins; one brother developed giantism due to a pituitary tumor. Hypersecretion of hGH during adulthood is called acromegaly (akЈ-roˉ-MEG-a-leˉ). Although hGH cannot produce further
lengthening of the long bones because the epiphyseal plates are
already closed, the bones of the hands, feet, cheeks, and jaws thicken
and other tissues enlarge. In addition, the eyelids, lips, tongue, and
FOCUS on HOMEOSTASIS
Glucocorticoids such as cortisol depress
inflammation and immune responses
Thymic hormones promote maturation of
T cells (a type of white blood cell)
Androgens stimulate growth of axillary
and pubic hair and activation of
Excess melanocyte-stimulating hormone
(MSH) causes darkening of skin
Epinephrine and norepinephrine dilate
(widen) airways during exercise and other
Erythropoietin regulates amount of
oxygen carried in blood by adjusting
number of red blood cells
Human growth hormone (hGH) and
insulinlike growth factors (IGFs) stimulate
Estrogens cause closure of the epiphyseal
plates at the end of puberty and help
maintain bone mass in adults
Parathyroid hormone (PTH) and calcitonin
regulate levels of calcium and other
minerals in bone matrix and blood
Thyroid hormones are needed for normal
development and growth of the skeleton
Epinephrine and norepinephrine help
increase blood flow to exercising muscle
PTH maintains proper level of Ca2+,
needed for muscle contraction
Glucagon, insulin, and other hormones
regulate metabolism in muscle fibers
hGH, IGFs, and thyroid hormones help
maintain muscle mass
Several hormones, especially thyroid
hormones, insulin, and growth hormone,
influence growth and development of the
PTH maintains proper level of Ca2+,
needed for generation and conduction of
Erythropoietin (EPO) promotes formation
of red blood cells
Aldosterone and antidiuretic hormone
(ADH) increase blood volume
Epinephrine and norepinephrine increase
heart rate and force of contraction
Several hormones elevate blood pressure
during exercise and other stresses
FOR ALL BODY SYSTEMS
Together with the nervous system, circulating
and local hormones of the endocrine system
regulate activity and growth of target cells
throughout the body
Several hormones regulate metabolism,
uptake of glucose, and molecules used for
ATP production by body cells
Epinephrine and norepinephrine depress
activity of the digestive system
Gastrin, cholecystokinin, secretin, and
peptide (GIP) help regulate digestion
Calcitriol promotes absorption of dietary
Leptin suppresses appetite
ADH, aldosterone, and atrial natriuretic
peptide (ANP) adjust the rate of loss of
water and ions in the urine, thereby
regulating blood volume and ion content
of the blood
Hypothalamic releasing and inhibiting
hormones, follicle-stimulating hormone
(FSH), and luteinizing hormone (LH)
regulate development, growth, and
secretions of the gonads (ovaries and
Estrogens and testosterone contribute to
development of oocytes and sperm and
stimulate development of secondary sex
Prolactin promotes milk secretion in
Oxytocin causes contraction of the uterus
and ejection of milk from the mammary
THE ENDOCRINE SYSTEM
Figure 18.22 Various endocrine disorders.
Disorders of the endocrine system often involve hyposecretion or hypersecretion of hormones.
(b) Acromegaly (excess hGH during adulthood)
(a) A 22-year-old man with pituitary giantism shown beside his
(d) Exophthalmos (excess thyroid
hormones, as in Graves disease)
(c) Goiter (enlargement of
(e) Cushing’s syndrome (excess
Which endocrine disorder is due to antibodies that mimic the action of TSH?
nose enlarge, and the skin thickens and develops furrows, especially
on the forehead and soles (Figure 18.22b).
The most common abnormality associated with dysfunction of the
posterior pituitary is diabetes insipidus (DI) (dıˉ-a-BEˉ-teˉz in-SIP-i-dus;
diabetes ϭ overflow; insipidus ϭ tasteless). This disorder is due to
defects in antidiuretic hormone (ADH) receptors or an inability to
secrete ADH. Neurogenic diabetes insipidus results from hyposecretion of ADH, usually caused by a brain tumor, head trauma, or brain
surgery that damages the posterior pituitary or the hypothalamus. In
nephrogenic diabetes insipidus, the kidneys do not respond to ADH.
The ADH receptors may be nonfunctional, or the kidneys may be
damaged. A common symptom of both forms of DI is excretion of
large volumes of urine, with resulting dehydration and thirst. Bedwetting is common in afflicted children. Because so much water is
lost in the urine, a person with DI may die of dehydration if deprived
of water for only a day or so.
Treatment of neurogenic diabetes insipidus involves hormone replacement, usually for life. Either subcutaneous injection or nasal
spray application of ADH analogs is effective. Treatment of nephrogenic diabetes insipidus is more complex and depends on the nature
of the kidney dysfunction. Restriction of salt in the diet and, paradoxically, the use of certain diuretic drugs, are helpful.
Thyroid Gland Disorders
Thyroid gland disorders affect all major body systems and are among
the most common endocrine disorders. Congenital hypothyroidism,
hyposecretion of thyroid hormones that is present at birth, has devastating consequences if not treated promptly. Previously termed cretinism, this condition causes severe mental retardation and stunted bone
growth. At birth, the baby typically is normal because lipid-soluble
maternal thyroid hormones crossed the placenta during pregnancy
and allowed normal development. Most states require testing of all
newborns to ensure adequate thyroid function. If congenital hypothyroidism exists, oral thyroid hormone treatment must be started soon
after birth and continued for life.
Hypothyroidism during the adult years produces myxedema (mixe-DEˉ-ma), which occurs about five times more often in females than
in males. A hallmark of this disorder is edema (accumulation of inter-
DISORDERS: HOMEOSTATIC IMBALANCES
Hypoparathyroidism (hıˉ-poˉ-parЈ-a-THIˉ-royd-izm)—too little parathyroid hormone—leads to a deficiency of blood Ca2ϩ, which causes
neurons and muscle fibers to depolarize and produce action potentials spontaneously. This leads to twitches, spasms, and tetany
(maintained contraction) of skeletal muscle. The leading cause of
hypoparathyroidism is accidental damage to the parathyroid glands
or to their blood supply during thyroidectomy surgery.
Hyperparathyroidism, an elevated level of parathyroid hormone, most often is due to a tumor of one of the parathyroid
glands. An elevated level of PTH causes excessive resorption of bone
matrix, raising the blood levels of calcium and phosphate ions and
causing bones to become soft and easily fractured. High blood calcium level promotes formation of kidney stones. Fatigue, personality
changes, and lethargy are also seen in patients with hyperparathyroidism.
Adrenal Gland Disorders
Hypersecretion of cortisol by the adrenal cortex produces
Cushing’s syndrome (Figure 18.22e). Causes include a tumor of
the adrenal gland that secretes cortisol, or a tumor elsewhere that
secretes adrenocorticotropic hormone (ACTH), which in turn stimulates excessive secretion of cortisol. The condition is characterized by breakdown of muscle proteins and redistribution of body
fat, resulting in spindly arms and legs accompanied by a rounded
“moon face,” “buffalo hump” on the back, and pendulous (hanging) abdomen. Facial skin is flushed, and the skin covering the
abdomen develops stretch marks. The person also bruises easily,
and wound healing is poor. The elevated level of cortisol causes
hyperglycemia, osteoporosis, weakness, hypertension, increased
susceptibility to infection, decreased resistance to stress, and
mood swings. People who need long-term glucocorticoid therapy—for instance, to prevent rejection of a transplanted organ—
may develop a cushingoid appearance.
Hyposecretion of glucocorticoids and aldosterone causes Addison’s
disease (chronic adrenocortical insufficiency). The majority of
cases are autoimmune disorders in which antibodies cause adrenal
cortex destruction or block binding of ACTH to its receptors.
Pathogens, such as the bacterium that causes tuberculosis, also may
trigger adrenal cortex destruction. Symptoms, which typically do
not appear until 90% of the adrenal cortex has been destroyed,
include mental lethargy, anorexia, nausea and vomiting, weight
loss, hypoglycemia, and muscular weakness. Loss of aldosterone
leads to elevated potassium and decreased sodium in the blood,
low blood pressure, dehydration, decreased cardiac output,
arrhythmias, and even cardiac arrest. The skin may have a “bronzed”
appearance that often is mistaken for a suntan. Such was true in
the case of President John F. Kennedy, whose Addison’s disease
was known to only a few while he was alive. Treatment consists of
replacing glucocorticoids and mineralocorticoids and increasing
sodium in the diet.
Usually benign tumors of the chromaffin cells of the adrenal
medulla, called pheochromocytomas (feˉ-oˉ-kroˉЈ-moˉ-si-TO¯-mas;
pheo- ϭ dusky; -chromo- ϭ color; -cyto- ϭ cell), cause hypersecretion of epinephrine and norepinephrine. The result is a prolonged version of the fight-or-flight response: rapid heart rate, high blood
pressure, high levels of glucose in blood and urine, an elevated
basal metabolic rate (BMR), flushed face, nervousness, sweating,
and decreased gastrointestinal motility. Treatment is surgical
removal of the tumor.
Pancreatic Islet Disorders
The most common endocrine disorder is diabetes mellitus (MEL-itus; melli- ϭ honey sweetened), caused by an inability to produce or
use insulin. Diabetes mellitus is the fourth leading cause of death by
disease in the United States, primarily because of its damage to the
cardiovascular system. Because insulin is unavailable to aid transport
of glucose into body cells, blood glucose level is high and glucose
“spills” into the urine (glucosuria). Hallmarks of diabetes mellitus are
the three “polys”: polyuria, excessive urine production due to an inability of the kidneys to reabsorb water; polydipsia, excessive thirst;
and polyphagia, excessive eating.
Both genetic and environmental factors contribute to onset of the
two types of diabetes mellitus—type 1 and type 2—but the exact
mechanisms are still unknown. Type 1 diabetes, previously known
as insulin-dependent diabetes mellitus (IDDM), occurs because the
person’s immune system destroys the pancreatic beta cells. As a result, the pancreas produces little or no insulin. Type 1 diabetes usually
develops in people younger than age 20 and it persists throughout
life. By the time symptoms of type 1 diabetes arise, 80–90% of the
islet beta cells have been destroyed. Type 1 diabetes is most common
in northern Europe, especially in Finland, where nearly 1% of the
population develops type 1 diabetes by 15 years of age. In the United
States, type 1 diabetes is 1.5–2.0 times more common in whites than
in African American or Asian populations.
The cellular metabolism of an untreated type 1 diabetic is similar to
that of a starving person. Because insulin is not present to aid the entry
of glucose into body cells, most cells use fatty acids to produce ATP.
Stores of triglycerides in adipose tissue are catabolized to yield fatty
acids and glycerol. The by-products of fatty acid breakdown—organic
acids called ketones or ketone bodies—accumulate. Buildup of ketones
causes blood pH to fall, a condition known as ketoacidosis (keˉЈ-toˉ-as¯ -sis). Unless treated quickly, ketoacidosis can cause death.
Parathyroid Gland Disorders
C H A P T E R
stitial fluid) that causes the facial tissues to swell and look puffy. A
person with myxedema has a slow heart rate, low body temperature,
sensitivity to cold, dry hair and skin, muscular weakness, general lethargy, and a tendency to gain weight easily. Because the brain has already reached maturity, mental retardation does not occur, but the
person may be less alert. Oral thyroid hormones reduce the symptoms.
The most common form of hyperthyroidism is Graves disease,
which also occurs seven to ten times more often in females than in
males, usually before age 40. Graves disease is an autoimmune disorder in which the person produces antibodies that mimic the action of
thyroid-stimulating hormone (TSH). The antibodies continually stimulate the thyroid gland to grow and produce thyroid hormones. A
primary sign is an enlarged thyroid, which may be two to three times
its normal size. Graves patients often have a peculiar edema behind
the eyes, called exophthalmos (ekЈ-sof-THAL-mos), which causes the
eyes to protrude (Figure 18.22d). Treatment may include surgical removal of part or all of the thyroid gland (thyroidectomy), the use of
radioactive iodine (131I) to selectively destroy thyroid tissue, and the
use of antithyroid drugs to block synthesis of thyroid hormones.
A goiter (GOY-ter; guttur ϭ throat) is simply an enlarged thyroid
gland. It may be associated with hyperthyroidism, hypothyroidism, or
euthyroidism (uˉ-THI¯ -royd-izm; eu ϭ good), which means normal
secretion of thyroid hormone. In some places in the world, dietary
iodine intake is inadequate; the resultant low level of thyroid hormone in the blood stimulates secretion of TSH, which causes thyroid
gland enlargement (Figure 18.22c).
THE ENDOCRINE SYSTEM
The breakdown of stored triglycerides also causes weight loss. As
lipids are transported by the blood from storage depots to cells, lipid
particles are deposited on the walls of blood vessels, leading to atherosclerosis and a multitude of cardiovascular problems, including cerebrovascular insufficiency, ischemic heart disease, peripheral vascular disease, and gangrene. A major complication of diabetes is loss of vision
due either to cataracts (excessive glucose attaches to lens proteins, causing cloudiness) or to damage to blood vessels of the retina. Severe
kidney problems also may result from damage to renal blood vessels.
Type 1 diabetes is treated through self-monitoring of blood glucose
level (up to 7 times daily), regular meals containing 45–50% carbohydrates and less than 30% fats, exercise, and periodic insulin injections
(up to 3 times a day). Several implantable pumps are available to provide insulin without the need for repeated injections. Because they
lack a reliable glucose sensor, however, the person must self-monitor
blood glucose level to determine insulin doses. It is also possible to
successfully transplant a pancreas, but immunosuppressive drugs must
then be taken for life. Another promising approach under investigation is transplantation of isolated islets in semipermeable hollow
tubes. The tubes allow glucose and insulin to enter and leave but prevent entry of immune system cells that might attack the islet cells.
Type 2 diabetes, formerly known as non-insulin-dependent
diabetes mellitus (NIDDM), is much more common than type 1, representing more than 90% of all cases. Type 2 diabetes most often occurs
in obese people who are over age 35. However, the number of obese
children and teenagers with type 2 diabetes is increasing. Clinical
symptoms are mild, and the high glucose levels in the blood often can
be controlled by diet, exercise, and weight loss. Sometimes, drugs
such as glyburide (DiaBeta®) and metformin (Fortamet®) are used to
stimulate secretion of insulin by pancreatic beta cells. Although some
type 2 diabetics need insulin, many have a sufficient amount (or even
a surplus) of insulin in the blood. For these people, diabetes arises not
from a shortage of insulin but because target cells become less sensitive to it due to down-regulation of insulin receptors.
Hyperinsulinism most often results when a diabetic injects too
much insulin. The main symptom is hypoglycemia, decreased blood
glucose level, which occurs because the excess insulin stimulates too
much uptake of glucose by body cells. The resulting hypoglycemia
stimulates the secretion of epinephrine, glucagon, and human
growth hormone. As a consequence, anxiety, sweating, tremor, increased heart rate, hunger, and weakness occur. When blood glucose
falls, brain cells are deprived of the steady supply of glucose they need
to function effectively. Severe hypoglycemia leads to mental disorientation, convulsions, unconsciousness, and shock. Shock due to an insulin overdose is termed insulin shock. Death can occur quickly unless
blood glucose is restored to normal levels. From a clinical standpoint,
a diabetic suffering from either a hyperglycemia or a hypoglycemia
crisis can have very similar symptoms—mental changes, coma, seizures, and so on. It is important to quickly and correctly identify the
cause of the underlying symptoms and treat them appropriately.
Gynecomastia (gıˉЈ-ne-koˉ-MAS-teˉ-a; gyneco- ϭ woman; -mast- ϭ
breast) Excessive development of mammary glands in a male.
Sometimes a tumor of the adrenal gland may secrete sufficient
amounts of estrogen to cause the condition.
Hirsutism (HER-soo-tizm; hirsut- ϭ shaggy) Presence of excessive
body and facial hair in a male pattern, especially in women; may
be due to excess androgen production due to tumors or drugs.
Thyroid crisis (storm) A severe state of hyperthyroidism that can be
life-threatening. It is characterized by high body temperature,
rapid heart rate, high blood pressure, gastrointestinal symptoms
(abdominal pain, vomiting, diarrhea), agitation, tremors, confusion, seizures, and possibly coma.
Virilizing adenoma (aden- ϭ gland; -oma ϭ tumor) Tumor of the
adrenal gland that liberates excessive androgens, causing virilism
(masculinization) in females. Occasionally, adrenal tumor cells
liberate estrogens to the extent that a male patient develops gynecomastia. Such a tumor is called a feminizing adenoma.
C H A P T E R R E V I E W A N D R E S O U R C E S U M M A RY
Anatomy Overview - The Endocrine
1. Hormones regulate the activity of smooth muscle, cardiac muscle, and some glands; alter metabolism; spur
growth and development; influence reproductive processes; and participate in circadian (daily) rhythms.
18.1 Comparison of Control by the Nervous and Endocrine Systems
1. The nervous system controls homeostasis through nerve impulses and neurotransmitters, which act
locally and quickly. The endocrine system uses hormones, which act more slowly in distant parts of the
body. (See Table 18.1.)
2. The nervous system controls neurons, muscle cells, and glandular cells; the endocrine system regulates
virtually all body cells.
18.2 Endocrine Glands
1. Exocrine glands (sudoriferous, sebaceous, mucous, and digestive) secrete their products through ducts
into body cavities or onto body surfaces. Endocrine glands secrete hormones into interstitial fluid. Then,
the hormones diffuse into the blood.
2. The endocrine system consists of endocrine glands (pituitary, thyroid, parathyroid, adrenal, and pineal
glands) and other hormone-secreting tissues (hypothalamus, thymus, pancreas, ovaries, testes, kidneys,
stomach, liver, small intestine, skin, heart, adipose tissue, and placenta).
Anatomy Overview - The Nervous
Anatomy Overview - The Endocrine
CHAPTER REVIEW AND RESOURCE SUMMARY
18.3 Hormone Activity
Anatomy Overview - Hormones
Anatomy Overview - Lipid-Soluble
Anatomy Overview - WaterSoluble Hormones
Anatomy Overview - Local
Animation - Mechanisms of
1. Lipid-soluble steroid hormones and thyroid hormones affect cell function by altering gene expression.
2. Water-soluble hormones alter cell function by activating plasma membrane receptors, which elicit production of a second messenger that activates various enzymes inside the cell.
3. Hormonal interactions can have three types of effects: permissive, synergistic, or antagonistic.
Homeostatic Control of Hormone Secretion
1. Hormone secretion is controlled by signals from the nervous system, chemical changes in blood, and
2. Negative feedback systems regulate the secretion of many hormones.
18.6 Hypothalamus and Pituitary Gland
1. The hypothalamus is the major integrating link between the nervous and endocrine systems. The
hypothalamus and pituitary gland regulate virtually all aspects of growth, development, metabolism,
and homeostasis. The pituitary gland is located in the hypophyseal fossa and is divided into two main
portions: the anterior pituitary (glandular portion) and the posterior pituitary (nervous portion).
2. Secretion of anterior pituitary hormones is stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus.
3. The blood supply to the anterior pituitary is from the superior hypophyseal arteries. Hypothalamic
releasing and inhibiting hormones enter the primary plexus and flow to the secondary plexus in the
anterior pituitary by the hypophyseal portal veins.
4. The anterior pituitary consists of somatotrophs that produce human growth hormone (hGH), lactotrophs
that produce prolactin (PRL), corticotrophs that secrete adrenocorticotropic hormone (ACTH) and
melanocyte-stimulating hormone (MSH), thyrotrophs that secrete thyroid-stimulating hormone (TSH),
and gonadotrophs that synthesize follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
(See Tables 18.3 and 18.4.)
5. Human growth hormone (hGH) stimulates body growth through insulinlike growth factors (IGFs).
Secretion of hGH is inhibited by GHIH (growth hormone–inhibiting hormone, or somatostatin) and
promoted by GHRH (growth hormone–releasing hormone).
6. TSH regulates thyroid gland activities. Its secretion is stimulated by TRH (thyrotropin-releasing hormone) and suppressed by GHIH.
7. FSH and LH regulate the activities of the gonads—ovaries and testes. Their secretion is controlled by
GnRH (gonadotropin-releasing hormone).
8. Prolactin (PRL) helps initiate milk secretion. Prolactin-inhibiting hormone (PIH) suppresses secretion
of PRL; prolactin-releasing hormone (PRH) stimulates PRL secretion.
9. ACTH regulates the activities of the adrenal cortex and is controlled by CRH (corticotropin-releasing
hormone). Dopamine inhibits secretion of MSH.
10. The posterior pituitary contains axon terminals of neurosecretory cells whose cell bodies are in the
hypothalamus. Hormones made by the hypothalamus and stored in the posterior pituitary are oxytocin
(OT), which stimulates contraction of the uterus and ejection of milk from the breasts, and antidiuretic
hormone (ADH), which stimulates water reabsorption by the kidneys and constriction of arterioles. (See
Table 18.5.) Oxytocin secretion is stimulated by uterine stretching and suckling during nursing; ADH
secretion is controlled by osmotic pressure of the blood and blood volume.
18.7 Thyroid Gland
1. The thyroid gland is located inferior to the larynx.
2. It consists of thyroid follicles composed of follicular cells, which secrete the thyroid hormones thyroxine (T4) and triiodothyronine (T3), and parafollicular cells, which secrete calcitonin (CT).
Animation – Introduction to Hormonal
Regulation, Secretion, and
Exercise - Hormone Actions
Animation - Introduction to Hormone
Exercise - Produce That Hormone
Anatomy Overview - The Hypothalamus
and Pituitary Gland
Anatomy Overview - Hormones of the
Anterior Pituitary Gland
Anatomy Overview - The Hypothalamus
Anatomy Overview - Hormones of the
Anatomy Overview - Hypothalamic
Animation - hGH: Growth and
Animation - GHRH/hGH
Animation - ACTH/Cortisol:
Animation - TRH/TSH: Production
Animation - hGH: Glycogenolysis and
Animation - Antidiuretic Hormonee
Figure 18.5 - Hypothalamus andd
Pituitary Gland and Their
Anatomy Overview - The Thyroid
Animation - Thyroid Hormones and
Glucose and Lipid Catabolism
Animation - TRH/TSH
18.4 Mechanisms of Hormone Action
C H A P T E R
1. Hormones affect only specific target cells that have receptors to recognize (bind) a given hormone. The
number of hormone receptors may decrease (down-regulation) or increase (up-regulation).
2. Circulating hormones enter the bloodstream; local hormones (paracrines and autocrines) act locally on
3. Chemically, hormones are either lipid-soluble (steroids, thyroid hormones, and nitric oxide) or watersoluble (amines; peptides, proteins, and glycoproteins; and eicosanoids). (See Table 18.2.)
4. Water-soluble hormone molecules circulate in the watery blood plasma in a “free” form (not attached to
plasma proteins); most lipid-soluble hormones are bound to transport proteins synthesized by the liver.
THE ENDOCRINE SYSTEM
3. Thyroid hormones are synthesized from iodine and tyrosine within thyroglobulin (TGB). They are
transported in the blood bound to plasma proteins, mostly thyroxine-binding globulin (TBG).
4. Secretion is controlled by TRH from the hypothalamus and thyroid-stimulating hormone (TSH) from
the anterior pituitary.
5. Thyroid hormones regulate oxygen use and metabolic rate, cellular metabolism, and growth and development.
6. Calcitonin (CT) can lower the blood level of calcium ions (Ca2ϩ) and promote deposition of Ca2ϩ into
bone matrix. Secretion of CT is controlled by the Ca2ϩ level in the blood. (See Table 18.6.)
18.8 Parathyroid Glands
1. The parathyroid glands are embedded in the posterior surfaces of the lateral lobes of the thyroid gland.
They consist of chief cells and oxyphil cells.
2. Parathyroid hormone (PTH) regulates the homeostasis of calcium, magnesium, and phosphate ions by
increasing blood calcium and magnesium levels and decreasing blood phosphate levels. PTH secretion
is controlled by the level of calcium in the blood. (See Table 18.7.)
18.9 Adrenal Glands
1. The adrenal glands are located superior to the kidneys. They consist of an outer adrenal cortex and inner
2. The adrenal cortex is divided into a zona glomerulosa, a zona fasciculata, and a zona reticularis; the
adrenal medulla consists of chromaffin cells and large blood vessels.
3. Cortical secretions include mineralocorticoids, glucocorticoids, and androgens.
4. Mineralocorticoids (mainly aldosterone) increase sodium and water reabsorption and decrease potassium reabsorption. Secretion is controlled by the renin–angiotensin–aldosterone (RAA) pathway and by
Kϩ level in the blood.
5. Glucocorticoids (mainly cortisol) promote protein breakdown, gluconeogenesis, and lipolysis; help
resist stress; and serve as anti-inflammatory substances. Their secretion is controlled by ACTH.
6. Androgens secreted by the adrenal cortex stimulate growth of axillary and pubic hair, aid the prepubertal
growth spurt, and contribute to libido.
7. The adrenal medulla secretes epinephrine and norepinephrine (NE), which are released during stress and
produce effects similar to sympathetic responses. (See Table 18.8.)
18.10 Pancreatic Islets
1. The pancreas lies in the curve of the duodenum. It has both endocrine and exocrine functions.
2. The endocrine portion consists of pancreatic islets or islets of Langerhans, made up of four types of
cells: alpha, beta, delta, and F cells.
3. Alpha cells secrete glucagon, beta cells secrete insulin, delta cells secrete somatostatin, and F cells
secrete pancreatic polypeptide.
4. Glucagon increases blood glucose level; insulin decreases blood glucose level. Secretion of both hormones is controlled by the level of glucose in the blood. (See Table 18.9.)
18.11 Ovaries and Testes
1. The ovaries are located in the pelvic cavity and produce estrogens, progesterone, and inhibin.
These sex hormones govern the development and maintenance of female secondary sex characteristics, reproductive cycles, pregnancy, lactation, and normal female reproductive functions. (See
2. The testes lie inside the scrotum and produce testosterone and inhibin. These sex hormones govern
the development and maintenance of male secondary sex characteristics and normal male reproductive
functions. (See Table 18.10.)
18.12 Pineal Gland and Thymus
1. The pineal gland is attached to the roof of the third ventricle of the brain. It consists of secretory cells
called pinealocytes, neuroglia, and endings of sympathetic postganglionic axons.
2. The pineal gland secretes melatonin, which contributes to setting the body’s biological clock (controlled
in the suprachiasmatic nucleus). During sleep, plasma levels of melatonin increase.
3. The thymus secretes several hormones related to immunity.
4. Thymosin, thymic humoral factor (THF), thymic factor (TF), and thymopoietin promote the maturation
of T cells.
Animation - Calcitonin
Figure 18.11 - Steps in the
Synthesis and Secretion of
Exercise - Calcium Homeostasis
Anatomy Overview - Parathyroid Glands
Anatomy Overview - Hormones of the
Animation - Parathyroid Hormone
Anatomy Overview - Adrenal Glands
Anatomy Overview - Hormones of the
Animation - Epinephrine/NE
Figure 18.15 - The Adrenal
Figure 18.16 - Regulation of
Anatomy Overviews: The Pancreas;
Hormones of the Pancreas
Animations: Glucagon; Insulin
Figure 18.18 - The Pancreas
Figure 18.19 - Secretion of
Glucagon and Insulin
Exercise - Glucose Regulation
Concepts and Connections - Blood
Anatomy Overviews: The Ovaries;
Ovarian Hormones; The Testes;
Animations: Hormonal Control of Male
Reproductive Function; Hormonal
Regulation of Female Reproductive
Exercises: Match the Female Hormones;
Match the Male Hormones
Anatomy Overview - The Pineal Gland