Saladin 6e Extended Outline
Chapter 17
The Endocrine System
I. Overview of the Endocrine System (pp. 634–637)
A. The body has four principal avenues of communication from cell to cell. (p. 634)
1. Gap junctions join single-unit smooth muscle, cardiac muscle, epithelial, and other
cells, allowing passage of nutrients, electrolytes, and signaling molecules via the
cytoplasm. (Fig. 5.28)
2. Neurotransmitters are released by neurons, diffuse across the synaptic cleft, and bind to
receptors.
3. Paracrines are secreted by one cell and diffuse to nearby cells of the same tissue and
stimulate them; they are sometimes called local hormones.
4. Hormones in the strict sense are chemical messengers transported by the bloodstream
that stimulate physiological responses of cells of another tissue or organ.
B. This chapter deals with hormones and some paracrine secretions. The glands, tissues, and cells
that secrete hormones are the endocrine system. (p. 634)
1. The study of this system is endocrinology.
2. The most familiar hormone sources are the endocrine glands, such as the pituitary,
thyroid, and adrenal glands, etc. (Fig. 17.1)
3. Hormones are also secreted by organs and tissues not usually thought of as glands,
such as the brain, heart, small intestine, bones, and adipose tissue.
C. The classical distinction between endocrine and exocrine glands has been the absence or
presence of ducts. (pp. 634–636)
1. Most exocrine glands secrete their products by way of a duct onto an epithelial surface.
(Fig. 5.32)
2. Endocrine glands, in contrast, are ductless and release their secretions into the
bloodstream. Hormones were originally called the body’s internal secretions, from which
the glands get their name.
3. Exocrine secretions have extracellular effects, whereas endocrine secretions have
intracellular effects, altering cell metabolism.
4. Endocrine glands have a high density of blood capillaries, which are of a highly
permeable type called fenestrated capillaries that have patches of large pores in their
walls.
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5. Some glands and secretory cells are not easily classified as one or the other type. For
example, liver cells behave as exocrine cells when they secrete bile, but they also secrete
hormones into the blood, along with other factors.
D. The nervous and endocrine systems complement each other rather than duplicate each other’s
functions. (pp. 636–637) (Table 17.1)
1. They differ in means of communication, which is both electrical and chemical in the
nervous system and solely chemical in the endocrine system. (Fig. 17.2)
2. The systems also differ in terms of response to stimuli or their cessation.
a. The nervous system responds to a stimulus in a few milliseconds, whereas
hormone release may occur from several seconds up to days after the stimulus.
b. When a stimulus ends, the nervous system stops responding almost
immediately, whereas endocrine effects may persist for several days or weeks.
c. Under long-term stimulation, most neurons adapt and response declines, but
endocrine system response is more persistent.
3. An efferent nerve fiber innervates only one organ and a limited number of cells, so its
effects are targeted, while in contrast, hormones circulate throughout the body and have
more widespread effects.
4. In terms of similarities, several chemicals function both as neurotransmitters and as
hormones, including norepinephrine, dopamine, thyrotroponin-releasing hormone, and
others.
a. Some hormones, such as oxytocin and ephinephrine, are secreted by
neuroendocrine cells—neurons that release secretions into the bloodstream.
b. Some hormones and neurotransmitters produce overlapping effects on the
same targets, such as glucagon and norepinephrine acting on the liver cells.
c. The two systems regulate each other—neurons can trigger hormone secretion,
and hormones can stimulate or inhibit neurons.
5. Both neurotransmitters and hormones depend on receptors on the receiving cells. The
specificity of target organs or cells allows selective action of circulating hormones.
E. In terms of nomenclature, many hormones are denoted by standard abbreviations. (p. 637)
(Table 17.2)
II. The Hypothalamus and Pituitary Gland (pp. 638–645)
A. The pituitary gland and hypothalamus have a more wide-ranging influence than any other part
of the endocrine system. (p. 638)
B. Anatomically, the pituitary is suspended from the floor of the hypothalamus. (pp. 638–640)
1. The hypothalamus is shaped like a flattened funnel and forms the floor and walls of the
third ventricle of the brain. (Figs. 14.2, 14.12b)
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2. The pituitary gland (hypophysis) is connected to the hypothalamus by a stalk
(infundibulum) and housed in a depression of the sphenoid bone, the sella turcica.
a. The gland is roughly the size and shape of a kidney bean, usually about
1.3 cm wide; it grows 50% larger in pregnancy.
b. It is composed of two structures, the adenohypophysis and the
neurohypophysis, which have independent origins and separate functions.
(Fig. 17.3)
i. The adenohypophysis arises from a hypophyseal pouch that grows
upward from the embryonic pharynx.
ii. The neurohypophysis arises as a downgrowth of the brain, the
neurohypophyseal bud.
c. The adenohypophysis constitutes the anterior three-quarters of the pituitary
and has two parts. (Figs. 17.4a, 17.5a)
i. The anterior lobe (pars distalis) is most distal to the stalk.
ii. The pars tuberalis is a small mass of cells that wraps around the
stalk.
iii. In the fetus, the pars intermedia is also present between the anterior
lobe and neurohypophysis but degenerates during later development.
d. The hypophyseal portal system connects the hypothalamus to the anterior lobe
of the adenohypophysis. (Fig. 17.4b)
i. It consists of a network of primary capillaries in the hypothalamus, a
group of veins called portal venules that travel down the stalk, and a
complex of secondary capillaries in the anterior pituitary.
ii. The hypothalamus controls the anterior pituitary by secreting
hormones into the primary capillaries.
e. The neurohypophysis constitutes the posterior one-quarter of the pituitary and
has three parts.
i. The median eminence is an extension of the floor of the brain.
ii. The infundibulum is the stalk mentioned earlier.
iii. The largest part is the posterior lobe (pars nervosa).
f. The neurohypophysis is nervous tissue and not a true gland. (Fig. 17.5b)
i. The nerve fibers arise from certain cell bodies in the hypothalamus
and pass down the stalk as the hypothalamo-hypophyseal tract to end in
the posterior lobe. (Fig. 17.4a)
ii. The hypothalamic neurons synthesize hormones and transport them
to the axons in the posterior pituitary, where they are stored until a
nerve signal from the same axons triggers release into the blood.
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C. Eight hormones are produced in the hypothalamus: six regulate the anterior pituitary and two
are stored in the posterior pituitary and released on demand. (pp. 640–641) (Fig. 17.4)
1. The first six are described as releasing hormones if they stimulate pituitary cells to
secrete hormones of their own, or inhibiting hormones if they suppress pituitary
secretion. (Table 17.3)
a. The releasing or inhibiting effect is identified in the names of the hormones.
For example, somastatin inhibits growth hormone, which is known as
somatotropin.
2. The other two hypothalamic hormones are oxytocin (OT) and antidiuretic hormone
(ADH).
a. OT comes mainly from neurons in the right and left paraventricular nuclei of
the hypothalamus, named because they lie in the walls of the third ventricle.
b. ADH comes mainly from the supraoptic nuclei, named for the location just
above the optic chiasm.
c. They are stored and released by the posterior pituitary and so are considered
posterior lobe hormones even though not synthesized there.
D. The six anterior pituitary hormones are summarized as follows. (pp. 641–642) (Table 17.4)
1. Follicle-stimulating hormone (FSH) is secreted by pituitary cells called gonadotropes.
a. In the ovaries, FSH stimulates secretion of ovarian sex hormones and the
development of follicles.
b. In the testes it stimulates sperm production.
2. Luteinizing hormone (LH) is also secreted by the gonadotropes; FSH and LH are
collectively termed gonadotropins.
a. LH stimulates ovulation in females; after ovulation the follicle becomes a
yellowish body termed the corpus luteum, from which LH gets its name.
b. LH also stimulates the corpus luteum to secrete progesterone.
c. In males, LH stimulates the testes to secrete testosterone.
3. Thyroid-stimulating hormone (TSH), or thyrotropin, is secreted by cells called
thyrotropes; it stimulates growth of the thyroid gland and secretion of thyroid hormone.
4. Adrenocorticotropic hormone (ACTH), or corticotropin, is secreted by cells called
corticotropes.
a. Its target organ is the adrenal cortex.
b. It stimulates the cortex to release glucocorticoids (especially cortisol), which
are involved in the stress response.
5. Prolactin (PRL) is secreted by cells called lactotropes (mammotropes).
a. PRL secretion increases during pregnancy but has no effect until after a
woman gives birth, when it stimulates the mammary glands to synthesize milk.
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b. In males, PRL makes the testes more sensitive to LH and thus enhances the
secretion of testosterone.
6. Growth hormone (GH), or somatotropin, is secreted by somatotropes, the most
numerous cells of the anterior pituitary.
a. The pituitary produces at least a thousand times as much GH as any other
hormone.
b. GH stimulates mitosis and cellular differentiation to promote tissue growth.
7. The anterior pituitary is thus involved in a chain of events linked by hormones. This
chain begins in the hypothalamus and ends with binding of hormones from the anterior
pituitary to target organs. (Fig. 17.6)
E. The pars intermedia is absent from the adult human pituitary but is present in other animals and
in the human fetus. (p. 642)
1. In other species it secretes melanocyte-stimulating hormone (MSH), which influences
pigmentation of the skin, hair, or feathers. It has no such function in humans, who do not
have circulating MSH.
2. Some anterior lobe cells derived from the fetal pars intermedia produce the polypeptide
proopiomelanocortin (POMC), which is not secreted but processed into smaller
fragments such as ACTH and endorphins.
F. The two posterior lobe hormones are ADH and OT, which are synthesized in the hypothalamus
and then transported to the posterior pituitary for storage. (pp. 642–643)
1. Antidiuretic hormone (ADH) increases water retention by the kidneys, reduces urine
volume, and helps prevent dehydration.
a. ADH also functions as a neurotransmitter and is usually called vasopressin or
arginine vasopressin (AVP) in neuroscience.
b. It is also called vasopressin because it can cause vasoconstriction, but the
concentration required is unnaturally high, so it is of doubtful significance
except in pathological states.
2. Oxytocin (OT) has a variety of reproductive functions ranging from intercourse to birth
to breast-feeding.
a. OT surges during sexual arousal and orgasm.
b. In childbirth, it stimulates labor contractions.
c. In lactating mothers, it stimulates the flow of milk from mammary gland acini
to the nipple.
d. It may also play a role in bonding between sexual partners and between
mother and infant.
G. The control of pituitary hormone secretion in terms of type, timing, and amount are regulated
by the hypothalamus, other brain centers, and feedback from target organs. (pp. 643–644)
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1. Hypothalamic control enables the brain to monitor conditions within and outside the
body and to stimulate or inhibit the pituitary anterior-lobe hormones appropriately.
a. In times of stress, the hypothalamus triggers ACTH secretion that leads to
secretion of cortisol and mobilization of materials for tissue repair.
b. During pregnancy, the hypothalamus induces prolactin secretion so a woman
will be prepared to lactate after giving birth.
2. The posterior pituitary is controlled by neuroendocrine reflexes—the release of
hormones in response to nervous system signals.
a. Dehydration raises the osmolarity of the blood, which detected by
hypothalamic neurons called osmoreceptors that trigger ADH release,
conserving water.
b. Excessive blood pressure stimulates stretch receptors in the heart and certain
arteries, and via another neuroendocrine reflex, ADH release is inhibited,
increasing urine output.
c. The suckling of an infant stimulates nerve endings in the nipple, sending
sensory signals to spinal cord, brainstem, and hypothalamus, and finally to the
posterior pituitary, causing release of OT and milk ejection.
d. Neuroendocrine reflexes can also involve higher brain centers, as when
hearing a baby’s cry stimulates a lactating woman to eject milk.
3. Feedback from target organs also regulates the pituitary and hypothalamus through
feedback loops.
a. Most often, this regulation occurs by negative feedback inhibition, in which
the hormone itself inhibits further secretion by binding to the pituitary or
hypothalamus. (Fig. 17.7)
b. In the pituitary–thyroid system, the feedback inhibition is as follows:
i. The hypothalamus secretes TRH.
ii. TRH stimulates the anterior pituitary to secrete TSH.
iii. TSH stimulates the thyroid to secrete TH.
iv. TH stimulates the metabolism of most cells throughout the body.
v. TH also inhibits the release of TSH by the pituitary.
vi. To a lesser extent, TH inhibits the release of TRH by the
hypothalamus.
c. Steps five and six are the negative feedback inhibition steps, and they ensure
that hormone secretion is kept within a certain limit (set point).
d. Feedback is not always inhibitory. OT triggers a positive feedback cycle
during labor that continues until the infant is born. (Fig. 1.12)
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H. Growth hormone is unlike other pituitary hormones in that it is not targeted to just one or a few
organs but has widespread effects on the body. (pp. 644–645)
1. GH directly stimulates tissues, especially cartilage, bone, muscle, and fat. It also
induces the liver and other tissues to produce insulin-like growth factors (IGF-I and IGFII), also known as somatomedins, which then stimulate target cells. (Fig. 17.6)
a. One effect of IGF is to prolong the action of GH. The half-life of GH is only 6
to 20 minutes, whereas that of IGFs is about 20 hours.
2. The mechanisms of GH–IGF action include the following four:
a. Protein synthesis.
i. Within minutes of its secretion, GH boosts the translation of existing
mRNA, and within a few hours it also boosts DNA transcription.
ii. It also enhances amino acid transport into cells.
iii. GH also suppresses protein catabolism.
b. Lipid metabolism.
i. GH stimulates adipocytes to catabolize fat and release fatty acids and
glycerol.
ii. By providing these fuels, GH makes it unnecessary for cells to
consume their proteins, which is called the protein-sparing effect.
c. Carbohydrate metabolism.
i. GH also has a glucose-sparing effect. Its role in mobilizing fatty acids
reduces the dependence of cells on glucose so they will not compete
with the brain.
ii. GH also makes more glucose available for glycogen synthesis and
storage.
d. Electrolyte balance.
i. GH promotes Na+, K+, and Cl– retention by the kidneys.
ii. GH enhances Ca2+ absorption by the small intestine.
3. The most conspicuous effect of GH are on bone, cartilage, and muscle growth,
especially during childhood and adolescence.
a. IGF-I accelerates bone growth at the epiphyseal plates and stimulates
multiplication of chondrocytes and osteogenic cells.
b. It increases protein deposition in the cartilage and bone matrix.
c. In adulthood it stimulates osteoblast activity and the appositional growth of
bone, influencing bone thickening and remodeling.
4. GH secretion fluctuates over the course of a day.
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a. The GH level in blood plasma rises to 20 nanograms per milliliter or higher
during the first 2 hours of deep sleep, and may reach 30 ng/mL in response to
vigorous exercise.
b. Smaller peaks occur after high-protein meals, but a high-carbohydrate meal
tends to suppress GH secretion.
c. Trauma, hypoglycemia, and other conditions also stimulate GH secretion.
5. GH levels decline gradually with age.
a. Average concentration is 6 ng/mL in adolescence, and one-quarter of that in
very old age.
b. At age 30, the average adult body is 10% bone, 30% muscle, and 20% fat. At
age 75, the average is 8% bone, 15% muscle, and 40% fat.
III. Other Endocrine Glands (pp. 645–653)
A. The pineal gland is attached to the roof of the third ventricle beneath the posterior end of the
corpus callosum. (p. 645) (Figs. 17.1, 17.4a)
1. Its name alludes to a shape resembling a pine cone.
2. A child’s pineal gland is about 8 mm long and 5 mm wide, but after age 7 it regresses,
a process called involution.
3. Pineal secretion peaks between the ages of 1 and 5 years and declines 75% by the end
of puberty.
4. The pineal gland’s function is somewhat mysterious; it may plan a role in establishing
circadian rhythms of physiological function.
a. During the night it synthesizes melatonin, a monoamine, from serotonin.
i. Melatonin has been implicated in some human mood disorders,
although the evidence is inconclusive.
ii. Its secretion fluctuates seasonally with changes in day length, and in
animals that have seasonal breeding cycles.
iii. Melatonin may suppress gonadotropin secretion, since removal of
the pineal gland from animals causes premature sexual maturation.
b. The pineal gland may regulate the timing of puberty in humans, but this has
not been conclusively demonstrated.
c. Pineal tumors cause premature puberty in boys, but they also damage the
hypothalamus, so it is inconclusive of what causes the effect.
B. The thymus is a bilobed gland in the mediastinum superior to the heart, behind the sternal
manubrium. It plays a role in the endocrine, lymphatic, and immune systems. (p. 645)
1. In the fetus and infant it is relatively large, sometimes protruding between the lungs
nearly as far of the diaphragm and extending upward in to the neck. (Fig. 17.8a)
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2. It continues to grow until 5 or 6 years od age. In adults it weighs about 20 g up to age
60 but becomes less glandular with age, remaining as a small fibrous and fatty remnant in
the elderly. (Fig. 17.8b)
3. The thymus is a site of maturation for T cells that are critically important for immune
defense.
4. It secretes thymopoietin, thymosin, and thymulin, which stimulate development of
other lymphatic organs and development and activity of T cells.
Insight 17.1 Melatonin, SAD, and PMS
C. The thyroid gland weighs about 25 g and is the largest endocrine gland in adults. It is
composed of two lobes that lie adjacent to the trachea immediately below the larynx (pp. 646–
647)
1. It is named for the shieldlike thyroid cartilage of the larynx.
2. Near the inferior end, the two lobes are usually joined by a narrow anterior bridge of
tissue, the isthmus. (Figs. 17.8, 17.9a)
3. It receives one of the highest rates of blood flow per gram of tissue and is dark reddish
brown in color. (Fig. 17.9a)
4. Histologically, it is composed mostly of sacs called thyroid follicles. (Fig. 17.9b)
a. Thyroid follicles are filled with a protein rich colloid and lined with a simple
cuboidal epithelium of follicular cells.
b. These cells secrete thyroxine (T 4, tetraiodothyronine) and triiodothryonine
(T3); they are collectively termed thyroid hormone (TH).
i. An average adult thyroid secretes 80 μg of TH daily, of which 98%
is T4.
ii. Most T4 is converted to T3 in target cells. T3 is the more
physiologically active form.
c. Thyroid hormone is secreted in response to TSH from the pituitary, and the
primary effect of TH is to increase the body’s metabolic rate.
d. TH raises oxygen consumption and has a calorigenic effect—it increases heat
production.
i. TH secretion rises in cold weather to help compensate for increased
heat loss. It raises respiratory rate, heart rate, and strength of heartbeat,
as well as stimulating the appetite.
ii. It also promotes alertness, reflex response, secretion of GH, growth
of bones, skin, hair, nails, and teeth, and development of the fetal
nervous system.
5. The thyroid gland also contains nests of C (clear) cells, or parafollicular cells, between
the follicles.
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a. These cells secrete calcitonin in response to rising levels of blood calcium,
which stimulates osteoblast activity and calcium deposition while antagonizing
the action of parathyroid hormone.
b. It is important mainly in children, having relatively little effect in adults.
D. The parathyroid glands are ovoid glands about 3 to 8 mm long and 2 to 5 mm wide. Four of
them are found partially embedded in the posterior surface of the thyroid, separated by a thin
fibrous capsule. (p. 647) (Fig. 17.10)
1. Sometimes they occur in other locations ranging from as high as the hyoid bone to as
low as the aortic arch; about 5% of people have more than four.
2. They secrete parathyroid hormone (PTH) in response to low blood calcium.
E. The adrenal (suprarenal) glands sit like caps on the superior surface of each kidney.
(pp. 647–650) (Fig. 17.11)
1. Like the kidneys, they are retroperitoneal.
2. The adult adrenal gland measures about 5 cm vertically, 3 cm wide, and 1 cm anterior
to posterior. It weighs about 8 to 10 g in the newborn, but by the age of 2 years following
involution of its outer layer, it becomes 4 to 5 g and remains this weight in adults.
3. The gland forms by the merger of two fetal glands with different origins and functions:
the gray to dark red adrenal medulla, 10% to 20% of the gland, and the yellowish adrenal
cortex, 80% to 90% of the gland.
4. The adrenal medulla has a dual nature, acting as both an endocrine gland and as a
ganglion of the sympathetic nervous system.
a. Sympathetic preganglionic nerve fibers extend through the cortex to reach
chromaffin cells in the medulla.
i. These cells have no dendrites or axon, and they release their products
into the bloodstream; they are considered neuroendocrine cells.
b. Upon stimulation by nerve fibers—usually under conditions of fear, pain or
stress—the chromaffin cells release catecholamines.
i. About three- quarters is epinephrine, one-quarter is norepinephrine,
and a trace is dopamine.
ii. These increase alertness and prepare the body for physical activity.
iii. They mobilize high energy fuels and boost glucose levels by
glycogenolysis and gluconeogenesis.
c. Epinephrine has a glucose-sparing effect in that it inhibits secretion of insulin,
so that muscles and other insulin-dependent organs absorb and consume less
glucose.
d. The adrenal catecholamines also raise heart rate and blood pressure, stimulate
circulation and pulmonary airflow, and raise metabolic rate.
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e. The catecholamines inhibit functions such as digestion and urine production.
5. The adrenal cortex, which surrounds the medulla, produces more than 25 steroid
hormones known as the corticosteroids or corticoids.
a. Only five of these are produced in physiologically significant amounts or
active forms.
b. These five fall into three categories, which are produced in three layers of
glandular tissue: mineralocorticoids by the zona glomerulosa; glucocorticoids by
the zona fasciculata; and sex steroids by the zona reticularis.
c. The zona glomerulosa is a thin layer located just beneath the capsule at the
gland surface.
i. Glomerulosa refers to the rounded clusters of cells in this zone.
ii. The zona glomerulosa mainly secretes aldosterone, a
mineralocorticoid that stimulates kidneys to retain sodium and excrete
potassium.
iii. Because water is retained along with sodium, aldosterone helps to
maintain blood volume and pressure.
d. The zona fasciculata is a thick middle layer constituting about three-quarters
of the adrenal cortex.
i. The cells in this zone are arranged in parallel cords (fascicles)
separated by blood capillaries, perpendicular to the gland surface.
ii. The cells are called spongiocytes because of the abundance of
cytoplasmic lipid droplets.
iii. The zona fasciculata secretes glucocorticoids in response to ACTH
from the pituitary, of which the most potent is cortisol
(hydrocortisone), although some effect is due to corticosterone.
iv. Glucocorticoids stimulate fat and protein catabolism,
gluconeogenesis, and the release of fatty acids and glucose into the
blood.
v. These hormones also have an anti-inflammatory effect and are used
to relieve swelling and other inflammation.
vi. Long-term secretion suppresses the immune system.
e. The zona reticularis is the narrow, innermost layer, adjacent to the renal
medulla.
i. Cells of this zone form a branching network (reticulum).
ii. They secrete sex steroids, including androgens and smaller amounts
of estrogen.
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iii. The adrenal androgens are dehydroepiandrosterone (DHEA) and
androstenedione, many tissues convert these to testosterone.
iv. DHEA is produced in tremendous quantities by the large adrenal
glands of the male fetus and plays an important role in prenatal
development of the reproductive tract.
v. In both sexes, androgens are responsible for development of
secondary sexual characteristics in puberty.
vi. In men, testosterone produced by the testes greatly overshadows that
converted from DHEA, but in women, DHEA provides about 50% of
the androgen requirement.
vii. The main adrenal estrogen is estradiol; this is of minor importance
to women during reproductive years, but is it is the main source of
estrogen after menopause.
6. The medulla and cortex are not as functionally independent as once thought; each of
them stimulates the other.
a. Without stimulation by cortisol, the adrenal medulla atrophies significantly.
b. Conversely, some chromaffin cells extend into the cortex, and when stress
activates the sympathetic nervous system, these cells stimulate the cortex to
secrete corticosterone.
F. The pancreas is an elongated, spongy, primarily exocrine gland below and behind the stomach
that secretes digestive enzymes—but scattered throughout its exocrine tissue are 1 to 2 million
endocrine cell clusters called pancreatic islets (islets of Langerhans). (pp. 650–651) (Fig. 17.12)
1. Although they are less than 2% of pancreatic tissue, the islets secrete hormones of vital
importance to glycemia, the blood glucose concentration.
2. An islet measures about 75 by 175 um and contains from a few to 3,000 cells, of which
about 20% are alpha cells, 70% are beta cells, 5% are delta cells, and a small number are
PP and G cells.
a. Alpha (α) cells, or A cells, secrete glucagons between meals when the blood
glucose concentration is falling.
i. In the liver, glucagons stimulates gluconeogenesis, glycogenolysis,
and the release of glucose into the circulation.
ii. In adipose tissue, it stimulates fat catabolism and the release of free
fatty acids.
iii. Glucagon is also secreted in response to rising amino acid levels
after a high-protein meal. It promotes amino acid absorption, providing
cells with raw material for gluconeogenesis.
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b. Beta (β) cells, or B cells, secrete insulin during or immediately following a
meal, when glucose and amino acid levels are rising.
i. Insulin stimulates cells to absorb these nutrients and store or
metabolize them.
ii. It promotes the synthesis of glycogen, fat, and protein, and thus the
storage of excess nutrients.
iii. It also antagonizes the effects of glucagons.
iv. Brain, liver, kidneys, and red blood cells absorb and use glucose
without insulin, but insulin does promote glycogen synthesis in the
liver.
v. Insulin insufficiency or inaction is the cause of diabetes mellitus.
c. Delta (δ) cell, or D cells, secrete somatostatin (growth hormone–inhibiting
hormone) concurrently with the release of insulin by the beta cells.
i. Somatostatin inhibits some digestive enzyme secretion and nutrient
absorption.
ii It acts locally in the pancreas as a paracrine secretion that modulates
other islet cells.
iii. It partially suppresses the secretion of glucagons and insulin by A
and B cells.
d. PP cells, or F cells, secrete pancreatic polypeptide that inhibits gallbladder
contraction and secretion of pancreatic digestive enzymes.
e. G cells secrete gastrin, which stimulates the stomach’s acid secretion,
motility, and emptying. The stomach and small intestine also secrete gastrin.
3. Any hormone that raises blood glucose level is called a hyperglycemic
hormone.Insulin is a hypoglycemic hormone because it lowers blood glucose level.
G. The gonads, ovaries and testes, are like the pancreas in that they are both endocrine and
exocrine. (pp. 651–652)
1. Their exocrine products are whole cells—eggs and sperm—and thus they are
sometimes called cytogenic glands.
2. Their endocrine products are the gonadal hormones, most of which are steroids.
3. The ovaries secrete chiefly estradiol, progesterone, and inhibin.
4. Each egg develops in its own follicle, which is lined by a wall of granulosa cells and
surrounded by a capsule, the theca. (Fig. 17.13a)
a. Theca cells synthesize androstenedione, and both theca and granulosa cells
convert this to estradiol and lesser amounts of estriol and estrone.
b. In the middle of the ovarian cycle, a mature follicle ruptures and releases the
egg.
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c. The remains of the follicle become the corpus luteum, which secretes
progesterone for the next 12 days in a typical cycle, or several weeks in the
event of pregnancy.
i. Inhibin, which is also secreted by the follicle and corpus luteum,
suppresses the secretion of FSH by the anterior pituitary.
d. The female gonadal hormones contribute to the development of the
reproductive system and female physique as well as promoting growth, and they
regulate the menstrual cycle, sustain pregnancy, and prepare the mammary
glands for lactation.
e. A testis consists mainly of seminiferous tubules that produce sperm.
f. Its endocrine secretions are testosterone, lesser amounts of other androgens
and estrogens, and inhibin.
i. Inhibin comes from sustentacular (Sertoli) cells that form the walls of
the seminiferous tubules.
ii. By limiting FSH secretion, inhibin regulates the rate of sperm
production.
g. Nestled between the tubules are clusters of interstitial cells (cells of Leydig),
the source of the gonadal steroids. (Fig. 17.13b)
h. Testosterone stimulates development of the male reproductive system in the
fetus and adolescent, development of the male physique in adolescence, and the
sex drive.
H. Several other tissues and organs secrete hormones or hormone precursors. (pp. 652–653)
1. The skin. Keratinocytes of the epidermis convert a cholesterol-like steroid into
cholecalciferol using UV radiation from the sun.
a. The liver and kidneys convert cholecalciferol to a calcium-regulating
hormone, calcitriol.
2. The liver. The liver is involved in production of at least five hormones.
a. It converts cholecalciferol into calcidiol, the next step in calcitriol synthesis.
b. It secretes angiotensinogen, a protein that is converted by kidneys, lungs, and
other organs into the hormone angiotensin II, which is a regulator of blood
pressure.
c. The liver secretes about 15% of the body’s erythropoietin (EPO), which
stimulates the production of red blood cells by the red bone marrow.
d. It secretes hepcidin, a recently discovered hormone involved in iron
homeostasis.
i. Hepcidin promotes intestinal absorption of dietary iron and
mobilization of iron for hemoglobin synthesis and other uses.
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e. The liver secretes insulin-like growth factor I (IGF-I), a hormone that
mediates the action of growth hormone.
3. The kidneys. The kidneys produce three hormones.
a. They convert calcidiol into calcitriol (vitamin D), which raises blood
concentration of calcium by promoting its intestinal absorption.
b. They secrete renin, an enzyme that converts angiotensinogen to angiotensin I.
i. As angiotensin I circulates, it is converted to angiotensin II by
angiotensin-coverting enzyme (ACE) in the linings of certain blood
capillaries. Angiotensin II constricts blood vessels and raises blood
pressure.
c. The kidneys secrete about 85% of the body’s erythropoietin.
3. The heart. Rising blood pressure stretches the heart wall and stimulates atrial muscle to
secrete atrial natriuretic peptide (ANP), and ventricle muscle to secrete brain natriuretic
peptide (BNP).
a. BNP was so named because it was first discovered in the brain. The heart
produces five times as much ANP as BNP.
b. Both peptides increase sodium excretion and urine output and oppose the
action of angiotensin II.
5. The stomach and small intestine. These contain enteroendocrine cells that secrete at
least ten eneteric hormones that coordinate actions of the digestive system.
a. Cholecystokinin (CCK) is secreted when fats arrive and stimulates the gall
bladder to release bile. It also acts as an appetite suppressant in the brain.
b. Gastrin is secreted by cells in the stomach upon arrival of food and stimulates
hydrochloric acid secretion.
c. Ghrelin is one of the enteric hormones that act on the hypothalamus; it is
secreted when the stomach is empty, producing the sensation of hunger.
d. Peptide YY (PYY), secreted by cells of the small and large intestines, signals
satiety.
6. Adipose tissue. Fat cells secrete the hormone leptin, which has long-term effects on
appetite-regulating centers of the hypothalamus.
a. A low level of leptin (low body fat) increases appetite, whereas a high level of
leptin (high body fat) tends to decrease appetite.
b. Leptin also serves as a signal for the onset of puberty, which is delayed in
persons with abnormally low body fat.
7. Osseous tissue. Osteoblasts secrete the hormone osteocalcin, which increases the
number of pancreatic beta cells, pancreatic output of insulin, and the insulin sensitivity of
other body tissues.
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a. Osteocalcin seems to inhibit fat deposition and the onset of type 2 diabetes
mellitus.
8. The placenta. This organ functions during pregnancy for fetal nutrition and waste
removal, but also secretes estrogen, progesterone, and other hormones that regulate
pregnancy and stimulate development of the fetus and mammary glands.
9. Endocrine organs and tissues other than the hypothalamus and pituitary are reviewed in
Table 17.5.
IV. Hormones and Their Actions (pp. 655–665)
A. Hormones fall into three chemical classes: steroids, peptides, and monoamines. (p. 655)
(Fig. 17.14) (Table 17.6)
1. Steroid hormones are derived from cholesterol.
a. They include the sex hormones and corticosteroids produced by the adrenal
gland.
b. Calcitriol, the calcium-regulating hormone, is not a steroid but is derived from
one and has the same character and mode of action as the steroids.
2. Monoamines (biogenic amines) are made from amino acids and retain an amino
group;,they include several neurotransmitters as well as hormones. (Fig. 12.21)
a. The monoamine hormones include dopamine, epinephrine, norepinephrine,
melatonin, and thyroid hormone.
b. Dopamine, epinephrine, and norepinephrine are called catecholamines.
3. Peptide hormones are chains of 3 to 200 or more amino acids.
a. Oxytocin and antidiuretic hormone, from the posterior pituitary, are very
similar, differing only in two of their nine amino acids. (Fig. 17.14c)
b. Except for dopamine, the releasing and inhibiting hormones of the
hypothalamus are polypeptides.
c. Most hormones of the anterior pituitary are polypeptides or glycoproteins.
d. Most glycoprotein hormones have an identical alpha chain of 92 amino acids
and a variable beta chain.
B. All hormones are synthesized from either cholesterol or amino acids, with carbohydrate added
in the case of glycoproteins. (pp. 656–660)
1. Steroid hormones are synthesized from cholesterol and differ mainly in the functional
groups attached to the four-ringed steroid backbone. (Fig. 17.15)
a. Although estrogen and progesterone are thought of as “female” hormones and
testosterone as a “male” hormone, they are interrelated in synthesis and have
roles in both sexes.
2. Peptide hormones are synthesized in the same way as any other protein.
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a. The gene is transcribed to form mRNA, and ribosomes translate the mRNA
and assemble amino acids in the right order to make the hormone.
b. The newly synthesized polypeptide is an inactive preprohormone
i. The first several amino acids serve as a signal peptide that guides it
into the cisterna of the rough endoplasmic reticulum.
ii. Here the signal peptide is split off and the remainder is now a
prohormone.
c. The prohormone is transferred to the Golgi complex which may process it
further and then package it for secretion.
d. Insulin begins as preproinsulin.
i. When the signal peptide is removed, the chain folds back on itself
and forms three disulfide bridges—it is now proinsulin.
ii. This is packaged into a secretory vesicle, where enzymes remove the
connecting (C) peptide.
iii. The remainder is now insulin, composed of two polypeptide chains
totaling 51 amino acids connected to each other by two of the three
disulfide bridges. (Fig. 17.16)
3. Monoamines are also made from amino acids.
a. Melatonin is synthesized from the amino acid tryptophan, and the other
monoamines from the amino acid tyrosine.
b. Thyroid hormone is unusual in that each molecule is composed of two
tyrosines.
c. The synthesis, storage, and secretion of thyroxine take place as follows:
(Fig. 17.17)
i. Follicular cells absorb iodide ions (I–) from the blood plasma and
secrete them into the follicle where the iodide is oxidized to
a reactive form.
ii. Meanwhile, the follicular cells synthesize thyroglobulin via the
rough ER and Golgi complex and release it onto the cell surface where
an enzyme at the plasma membrane adds iodine to some of its
tyrosines.
a. Each thyroglobin has 123 tyrosines in its amino acid chain
but only 4 to 8 of them will become thyroid hormone.
iii. In the lumen, tyrosines link to each other to form thyroxine (T 4), but
T4 remains bound to thyroglobulin. Stored thyroglobulin forms colloid.
(Fig. 17.9b)
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iv. When stimulated by TSH, follicular cells absorb droplets of
thyroglobulin by pinocytosis. A lysosome fuses with the vesicle and
releases an enzyme that liberates T 4 from the thyroglobulin.
v. Thyroxine is released into the blood and binds with transport
proteins that carry it to its target cells.The thyroid synthesizes a small
amount (5% of total) of triiodothyronine (T 3).
d. Iodine and tyrosine are combined in the follicular lumen by the following
processes. (Fig. 17.18)
i. An iodine atom binds to the tyrosine ring, converting it to
monoiodotyrosine (MIT).
ii. MIT binds a second iodine, becoming diiodotyrosine (DIT).
iii. Two DITs become linked through an oxygen atom of one of their
rings, forming thyroxine (T 4). The rest of the peptide chain splits away
from one of the tyrosines, but the thyroxine remains temporarily bound
to thyroglobulin through the other tyrosine.
iv. When the cell is singaled to release thyroid hormone, the lysosomal
enzyme degrades the peptide chain of thyroglobulin and releases
thyroxine.
e. T3 is synthesized in small amounts by the binding of an MIT and a DIT. Most
T3, however, is produced in the liver and other tissues by removing an iodine
from circulating T4.
C. Hormone transport through the blood, which is mostly water, is a simple matter of monoamines
and peptides, but the hydrophobic steroids and thyroid hormone must bind to hydrophilic transport
proteins. (p. 660)
1. Albumins and globulins synthesized by the liver act as transport proteins.
2. A hormone attached to a transport protein is called bound hormone, and the one that is
not attached is an unbound or free hormone.
3. Only the unbound hormone can leave a blood capillary and get to a target cell.
(Fig. 17.19)
4. Unbound hormone can be broken down or removed from the blood in a few minutes,
whereas bound hormone may circulate for hours to weeks.
5. Thyroid hormone binds to three transport proteins: albumin, thyretin (an albumin-like
protein), and an alpha globulin names thyroxine-binding globulin (TBG).
a. TBG binds the greatest amount.
b. More than 99% of circulating TH is bound.
6. Steroid hormones bind to globulins such as transcortin, the transport protein for
cortisol.7. Aldosterone is unusual in that it has no specific transport protein but binds
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weakly to albumin and others; however, 85% remains unbound and thus it has a half-life
of only 20 minutes.
Insight 17.2 Hormone Receptors and Therapy
D. Hormones stimulate only those cells that have receptors for them, and the receptors act like
switches to turn certain metabolic pathways on or off when the hormone binds to them.
(pp. 660–663)
1. Receptor–hormone interactions are similar to enzyme–substrate interactions. Unlike
enzymes, receptors do not chemically change their ligands; they do, however, exhibit
specificity and saturation.
a. Specificity means that a receptor for one hormone will not bind other
hormones.
b. Saturation is the condition in which all receptor molecules are occupied by
hormone molecules.
2. Steroid hormones and thyroid hormone enter the target cell nucleus and act directly on
the genes by activating or inhibiting transcription.
a. Steroid hormones are hydrophobic and diffuse easily through the plasma
membrane.
b. Most pass directly into the nucleus, but glucocorticoids bind to a receptor in
the cytosol, and the complex is then transported into the nucleus.
c. Estrogen and progesterone both act on cells of the uterine mucosa in a way
typical of steroids.
i. Estrogen activates a gene for the protein that functions as the
progesterone receptor.
ii. Progesterone binds to these receptors later, stimulating transcription
of the gene for a glycogen-synthesizing enzyme.
iii. The uterine cell then synthesizes and accumulates glycogen for the
nourishment of an embryo in the case of pregnancy.
iv. Progesterone has no effect on these cells unless estrogen has been
there earlier.
d. Thyroid hormone in the T4 form has little metabolic effect, but in the target
cell cytoplasm, an enzyme converts T 4 to the more potent T3.
i. T3 enters the target cell nucleus and binds to receptors. (Fig. 17.20)
ii. One of the genes activated by T 3 is for the enzyme Na+-K+ ATPase,
the sodium–potassium pump. One of the effects of this pump is to
generate heat.
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iii. T3 also activates transcription of genes for β-adrenergic receptors
and a component of myosin, enhancing cell responsiveness to
sympathetic nervous system stimulation.
e. Steroids and thyroid hormones typically require several hours to days to show
an effect, due to the lag time for transcription, translation, and accumulation of
protein.
3. Peptides and catecholamines are hydrophilic and cannot penetrate into a target cells, so
they bind to cell-surface receptors linked to second-messenger systems. (Fig. 17.19)
a. Glucagon binds to receptors on the surface of a liver cell, which activates a G
protein.
i. This G protein in turn activates adenylate cyclase to produce cAMP,
a second messenger.
ii. cAMP ultimately activates enzymes that hydrolyze glycogen.
(Fig. 17.21)
b. Somatostatin inhibits cAMP synthesis.
c. Atrial natriuretic peptide (ANP) works through cyclic guanosine
monophosphate (cGMP).
d. Second messengers do not linger in the cell, but are quickly broken down. For
example, cAMP is broken down by phosphodiesterase.
e. Other commonly employed second messengers include diacylglycerol
(diglyceride; DAG) and inositol triphosphate (IP 3).
f. The DAG pathway follows the steps on the left side of Fig. 17.22:
i. (1) A hormone binds to a receptor, which activates a G protein.
ii. (2) The G protein migrates to a phospholipase molecule and
activates it.
iii. (3) Phospholipase removes the phosphate-containing group from the
head of a membrane phospholipid, leaving DAG embedded in the
plasma membrane.
iv. (4) DAG activates protein kinase (PK) that phosphorylates enzymes.
g. The IP3 pathway follows the steps on the right side of Fig. 17.22. The first
two steps are the same as in the DAG pathway, and the new steps are:
i. (5) The phosphate-containing group removed at step 3 is IP 3, which
raises calcium concentration in the cytosol in two ways:
ii. (6) IP3 opens gated channels and admits Ca2+.
iii. (7) IP3 opens gated channels in the sarcoplasmic reticulum and
releases Ca2+ from storage. Calcium, a third messenger, can have three
effects:
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iv. (8) Ca2+ may bind to other gated membrane channels and alter the
potential or permeability.
v. (9) Ca2+ may activate cytoplasmic enzymes that alter metabolism.
vi. (10) Ca2+ may bind to calmodulin which in turn activates a protein
kinase (step 4).
h. In this way, hydrophilic hormones that cannot enter the cell can have marked
effects on metabolic activity by binding to a surface receptor.
i. Hormonal effects mediated through surface receptors are relatively quick
because the cell does not have to synthesize new proteins.
j. A hormone may employ more than one second messenger.
i. ADH uses the IP3-calcium system in smooth muscle but the cAMP
system in kidney tubules.
k. Insulin is different in that it binds to a plasma membrane enzyme, tyrosine
kinase, which directly phosphorylates cytoplasmic proteins.
E. One hormone molecule can trigger synthesis of an enormous number of enzyme molecules, a
mechanism called enzyme amplification. (pp. 663–664) (Fig. 17.23)
1. One glucagon molecule can ultimately result in the production of 1 billion enzyme
molecules.
2. Hormones are therefore potent in very low concentrations, and target cells do not need
a great number of hormone receptors.
F. Target cells can modulate their sensitivity to a hormone by up-regulation and down-regulation
of receptors. (p. 664)
1. In up-regulation, a cell increases the number of receptors, becoming more sensitive to
a hormone. (Fig. 17.24a)
2. In down-regulation, a cell reduces its receptor number and becomes less sensitive to a
hormone. (Fig. 17.24b)
3. Hormone therapy often involves long-term use of abnormally high pharmacological
doses of a hormone, which may have undesirable effects. For example, hydrocortisone
negatively affects bone metabolism.
4. These effects can come about in two ways:
a. Excess hormone may bind to receptor sites for other, related hormones and
mimic their effects.
b. A target cell may convert one hormone into another, such as testosterone into
estrogen.
G. Hormones may interact with one another because many hormones are present in the blood at
any time; their interactive effects may be grouped into three classes. (pp. 664–665)
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1. Synergistic effects—two or more hormones act together to produce an effect greater
than the sum of their separate effects.
2. Permissive effects—one hormone enhances the target organ’s response to a second
hormone secreted later, such as the effect of estrogen on up-regulation of progesterone
receptors in the uterus.
3. Antagonistic effects—one hormone opposes the action of another, such as insulin and
glucagon.
H. Hormone clearance occurs when hormones are taken up and degraded by the liver and kidneys
and then excreted in bile or urine. (p. 665)
1. The rate of hormone removal is the metabolic clearance rate (MCR).
2. The length of time required to clear 50% of the hormone from the blood is its half-life.
V. Stress and Adaptation (pp. 665–666)
A. Stress is any situation that upsets homeostasis and threatens an individual’s physical or
emotional well-being. (p. 665)
B. The body reacts to stress with the stress response or general adaptation syndrome (GAS). This
typically involves elevated levels of epinephrine and glucocorticoids, especially cortisol.
(p. 665)
C. Hans Selye showed that GAS occurs in three stages: the alarm reaction, the stage of resistance,
and the stage of exhaustion. (p. 665)
D. The alarm reaction is the initial response to stress and is mediated mainly by norepinephrine
from the sympathetic nervous system and epinephrine from the adrenal medulla. (p. 665)
1. These catecholamines prepare the body to take action such as when fighting or
escaping.
2. The consumption of stored glycogen occurs, which is important to transition to the
next stage.
3. Adosterone and angiotensin also increase, raising blood pressure and promoting water
conservation.
E. The stage of resistance is entered when the glycogen reserves are depleted, and the first priority
is to provide alternative fuels for metabolism; cortisol dominates this stage. (pp. 665–666)
1. The hypothalamus secretes corticotropin-releasing hormone (CRH); the pituitary then
releases adrenocorticotropic hormone (ACTH)and the adrenal cortex then releases
cortisol and other glucocorticoids.
2. Cortisol promotes breakdown of fat and protein into glycerol, fatty acids, and amino
acids, so that the liver can perform gluconeogenesis.
3. Cortisol also inhibits glucose uptake (glucose-sparing action) and protein synthesis.
a. Inhibition of protein synthesis has an adverse effect on the immune system.
i. Mast cells release histamine and other inflammatory chemicals.
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ii. Wounds heal poorly and a person becomes susceptible to infections.
iii. Ulcers may occur due to reduced resistance to bacteria and reduced
secretion of gastric mucus and pancreatic bicarbonate, suppressed by
epinephrine.
4. Cortisol suppresses the secretion of sex hormones.
F. The stage of exhaustion sets in when the body’s fat reserves are depleted and stress overwhelms
homeostasis. (p. 666)
1. This stage may be marked by rapid decline and death.
2. With fat stores gone, the body relies primarily on protein breakdown to meet energy
needs, accompanied by wasting away of the muscles and weakening.
3. The adrenal cortex may stop producing glucocorticoids.
4. A state of hypertension may be the result of aldosterone.
5. Aldosterone also hastens elimination of potassium and hydrogen ions, creating a state
of hypokalemia and alkalosis that can lead to nervous and muscular system dysfunctions.
VI. Eicosanoids and Paracrine Signaling (p. 666)
A. Paracrine messengers are chemical signals released by cells into the tissue fluid; they do not
travel by way of the blood but diffuse to nearby cells in the same tissue. (p. 670)
1. Histamine is released by mast cells alongside blood cells in connective tissue, and it
diffuses to the smooth muscle of the blood vessel causing dilation.
2. Nitric oxide is released by endothelial cells of the blood vessel itself and also causes
vasodilation.
3. In the pancreas, somatostatin released by delta cells acts as a paracrine signal when it
diffuses to alpha and beta cells, inhibiting their secretion of glucagon and insulin.
4. Catecholamines diffuse from adrenal medulla to cortex to stimulate corticosterone
secretion.
B. The eicosanoids are an important family of paracrine secretions. (p. 666)
1. These compounds have 20-carbon backbones derived from arachidonic acid, a
polyunsaturated fatty acid.
2. Some peptide hormones and other stimuli liberate arachidonic acid from a
phospholipid of the plasma membrane, and then two enzymes convert it to eicosanoids.
(Fig. 17.25)
a. Lipoxygenase helps convert arachidonic acid to leukotrienes, eidcosanoids
that mediate allergic and inflammatory reactions.
b. Cyclooxygenase converts arachidonic acid to three other types of eicosanoids.
i. Prostacyclin is produced by walls of blood vessels, where it inhibits
blood clotting and vasoconstriction.
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ii. Thromboxanes are produced by platelets and override prostacyclin to
stimulate vasoconstriction and clotting.
iii. Prostaglandins are a diverse group of eicosanoids that contain a
five-sided ring structure and were first found in semen and the prostate
gland. They are named PG plus a third letter indicating type of ring
structure, plus a subscript indicating number of double bonds, for
example PGF2α. (Fig. 17.25) (Table 17.7)
3. The action of some familiar drugs such as NSAIDs is due to their effect on the
pathways of eicosanoid synthesis.
Insight 17.3 Anti-Inflammatory Drugs
VII. Endocrine Disorders (pp. 667–671)
A. Hyposecretion is inadequate hormone release, and hypersecretion is excessive hormone release.
(p. 668)
1. If the hypothalamo–hypophyseal tract is severed, such as by a fractured sphenoid,
transport of oxytocin and ADH to the posterior pituitary is disrupted, leading to diabetes
insipidus.
2. Autoimmune diseases also can lead to hormone hyposecretion when endocrine cells
are attacked. This is one of the causes of diabetes mellitus.
3. Some tumors result in overgrowth of functional endocrine tissue and hypersecretion. A
pheochromocytoma, a tumor of the adrenal medulla, can cause hypersecretion of
epinephrine and norepinephrine. (Table 17.8)
4. Some autoimmune disorders can cause hypersecretion, such as toxic goiter (Graves
disease. (Table 17.8)
B. Pituitary disorders affect growth. (p. 668)
1. Hypersecretion of growth hormone (GH) in adults causes acromegaly. (Fig. 17.26)
2. GH hypersecretion in childhood or adolescence causes gigantism.
3. GH hyposecretion in childhood or adolescence causes pituitary dwarfism. (Table 17.8)
a. Pituitary dwarfism is rarer now that genetically engineered human GH is
available.
C. Thyroid and parathyroid disorders are discussed together because of these glands’ proximity.
(pp. 668–669)
1. Congenital hypothyroidism is hyposecretion of TH present from birth.
2. Severe or prolonged adult hypothyroidism can cause myxedema. Both congenital and
adult hypothyroidism can be treated with oral thyroid hormone.
3. A goiter is a pathological enlargement of the thyroid.
a. Endemic goiter is due to a dietary deficiency of iodine, required for TH
synthesis. (Fig. 17.27)
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b. Without TH, the pituitary produces extra TSH, and the thyroid gland
undergoes hypertrophy.
4. The parathyroids are sometimes accidentally removed in thyroid surgery.
a. Without hormone replacement, hypoparathyroidism causes a rapid decline in
calcium levels leading to fatal tetany within 3 or 4 days.
b. Hyperparathyroidism usually results from a tumor. It causes bone to become
soft and fragile, and raises the blood levels of calcium and phosphate, promoting
renal calculi (kidney stones) formed of calcium phosphate.
D. Adrenal disorders include Cushing syndrome and adrenogenital syndrome. (p. 669)
1. Cushing syndrome is excess cortisol secretion due to any of several causes, including
ACTH hypersecretion by the pituitary, ACTH-secreting tumors, or hyperactivity of the
adrenal cortex.
2. Cushing syndrome disrupts carbohydrate and protein metabolism, leading to
hyperglycemia, hypertension, muscle weakness, and edema.
a. Muscle and bone mass are lost as protein is catabolized.
b. Abnormal fat deposition between the shoulders or in the face may also occur,
and these may also be effects of long-term hydrocortisone therapy. (Fig. 17.28)
3. Adrenogenical syndrome (AGS) is the hypersecretion of adrenal androgens and
commonly accompanies Cushing syndrome.
a. In children, AGS often causes enlargement of the penis or clitoris and the
premature onset of puberty.
b. Prenatal AGS can result in newborn girls exhibiting masculinized genitalia
and being misidentified as boys. (Fig. 17.29)
c. In women, AGS produces masculinizing effects such as increased body hair,
deepening of the voice, and beard growth.
E. Diabetes mellitus is the world’s most prevalent metabolic disease, occurring in about 7% of the
U.S. population and even more in Scandinavia and the Pacific Islands (pp. 670–671)
1. It is the leading cause of adult blindness, renal failure, gangrene, and limb amputations.
2. Diabetes mellitus (DM) can be defined as a disruption of carbohydrate, fat, and protein
metabolism resulting from hyposecretion or inaction of insulin.
a. Classic signs are the three polys: polyuria (excessive urine), polydipsia
(intense thirst), and polyphagia (ravenous hunger).
b. Three further clinical signs are revealed by blood and urine tests:
hyperglycemia (elevated blood glucose), glycosuria (glucose in the urine, from
which the disease gets its name), and ketonuria (ketones in the urine).
3. Normally the kidneys remove glucose from the urine and return it to the blood, via
glucose transporters (carrier-mediated transport).
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4. In DM, the amount of glucose saturates the glucose transporters, and the excess
glucose passes through into the urine.
5. Glucose and ketones in urine raise osmolarity, causing osmotic diuresis—water
remains in the tubules.
6. A person with untreated DM may pass 10 to 15 L of urine per day, compared with 1 or
2 L normally.
7. There are two forms of DM: type 1 (formerly juvenile or insulin-dependent) and type 2
(formerly adult or non-insulin-dependent). The older terms have been abandoned because
they are misleading given current knowledge.
8. Type 1 DM accounts for 5% to 10% of all cases in the U.S.
a. Several genes have been identified that predispose a person to type 1 DM.
b. When a genetically susceptible individual is infected by certain viruses, the
body produces autoantibodies that destroy pancreatic beta cells.
c. When 80% to 90% of the beta cells are gone, insulin falls to a critically low
level and hyperglycemia occurs.
d. Victims require insulin to survive, usually by injection, and meal planning,
exercise, and self-monitoring of blood glucose are aspects of treatment.
e. It is usually diagnosed before age 30, but may occur later.
9. Type 2 DM accounts for 90% to 95% of all cases.
a. The chief problem is insulin resistance—unresponsiveness of the target cells
to the hormones.
b. There is clear evidence of a hereditary component because of differences in
incidence from one ethnic group to another.
i. Incidence is high among people of Native American, Hispanic, and
Asian descent.
ii. It also has a tendency to run in families and has high concordance in
genetically identical twins.
c. Age, obesity, and a sedentary lifestyle are important risk factors.
i. As muscle mass is replaced with fat, a person become less able to
regulate blood glucose level.
d. Type 2 DM develops slowly and is usually diagnosed after age 40, but is
becoming more prevalent in young people because of childhood obesity.
e. Another factor besides the effects of muscle loss is that adipose tissue secretes
chemical signals that directly interfere with glucose transport into most cells.
f. Type 2 DM can often be successfully managed through a weight loss program
of diet and exercise; if these prove inadequate, insulin therapy is also employed.
10. Pathogenesis results from a combination of cell starvation and hyperglycemia.
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a. The body metabolizes fat and protein when cells cannot absorb glucose.
b. Prior to insulin therapy, victims wasted away in pain, hunger, and despair.
Children lived less than 1 year after diagnosis.
c. Rapid fat catabolism elevates blood levels of free fatty acids and their
breakdown products, the ketone bodies, and leads to ketonuria.
i. Ketonuria flushes Na+ and K+ from the body, creating electrolyte
deficiencies.
ii. Ketones in the blood lower the pH, causing ketoacidosis and a deep
gasping breathing called Kussmaul respiration, typical of terminal
diabetes. Ketoacidosis also produces diabetic coma.
d. DM leads to long-term degenerative cardiovascular disease.
i. Chronic hyperglycemia has negative effects on small to medium
blood vessels (microvascular disease) including atherosclerosis.
ii. Two common complications are blindness and renal failure, brought
on by arterial degeneration in retinas and kidneys.
iii. Death by renal failure is more common in type 1 than in type 2.
iv. In type 2, death due to heart failure from coronary artery disease is
more common.
e. DM leads to long-term degenerative neurological disease.
i. Diabetic neuropathy is nerve damage resulting from impoverished
blood flow.
ii. This can lead to loss of sensation, incontinence, and erectile
dysfunction.
iii. Microvascular disease in the skin results in poor healing, so that
even a minor break easily becomes infected and even gangrenous,
especially in the feet.
iv. Neuropathy may make a person unaware of skin lesions so that they
are not treated quickly.
11. Other types of diabetes exist, such as diabetes insipidus, described earlier.
Insight 17.4 The Discovery of Insulin
Connective Issues: Endocrine System Interactions
Cross References
Additional information on topics mentioned in Chapter 17 can be found in the chapters listed below.
Chapter 1: Oxytocin and positive feedback cycles
Chapter 2: Enzyme–substrate interactions
Chapter 3: Effects of the sodium–potassium pump
Saladin Outline Ch.17
Chapter 5: Exocrine glands
Chapter 7: Mechanisms of parathyroid hormone action
Chapter 12: Monoamines (biogenic amines) as neurotransmitters
Chapter 14: Hypothalamus structure and function
Chapter 18: Prostacyclin and thromboxane action
Chapter 21: The histology and immune functions of the thymus
Chapter 21: Eicosanoids and allergic and inflammatory reactions
Chapter 23: Other forms of diabetes
Chapter 26: Leptin and enteric hormone action
Chapters 27, 28: Anatomy of gonads
Chapter 28: Functions of estradiol and progesterone
Page 28