Mader: Understanding III. Integration and 10.

The Endocrine System © The McGraw−Hill

Human Anatomy & Coordination Companies, 2004
Physiology, Fifth Edition

chapter

The Endocrine System

Pancreatic islets (light

pink areas) are shown
in this photomicrograph
of the pancreas.

chapter outline & learning objectives After you have studied this chapter, you should be able to:

10.1 Endocrine Glands (p. 186) 10.4 Adrenal Glands (p. 193) 10.7 Chemical Signals (p. 201)
■ Define a hormone, and state the function of ■ Describe the anatomy of the adrenal glands. ■ Discuss the difference in mode of action
hormones. ■ Discuss the function of the adrenal medulla between peptide and steroid hormones.
■ Name the major endocrine glands, and and its relationship to the nervous system. ■ Give examples to show that chemical signals
identify their locations. ■ Name three categories of hormones produced can act between organs, cells, and
■ Discuss the control of glandular secretion by by the adrenal cortex, give an example of each individuals.
negative feedback. category, and discuss their actions.
10.8 Effects of Aging (p. 202)
10.2 Hypothalamus and Pituitary 10.5 Pancreas (p. 196) ■ Discuss the anatomical and physiological
Gland (p. 188) ■ Describe the anatomy of the pancreas. changes that occur in the endocrine system as
we age.
■ Explain the anatomical and functional ■ Name two hormones produced by the
relationships between the hypothalamus and pancreas, and discuss their functions. 10.9 Homeostasis (p. 202)
the pituitary gland. ■ Discuss the two types of diabetes mellitus, ■ Discuss how the endocrine system works with
■ Name and discuss two hormones produced by and contrast hypoglycemia with other systems of the body to maintain
the hypothalamus that are secreted by the hyperglycemia. homeostasis.
posterior pituitary.
■ Name the hormones produced by the anterior 10.6 Other Endocrine Glands Visual Focus
pituitary, and indicate which of these control (p. 198) The Hypothalamus and the Pituitary (p. 189)
other endocrine glands. ■ Name the most important male and female

10.3 Thyroid and Parathyroid sex hormones. Discuss their functions. Medical Focus
■ Discuss atrial natriuretic hormone, growth Side Effects of Anabolic Steroids (p. 199)
Glands (p. 191) factors, and prostaglandins as hormones not Glucocorticoid Therapy (p. 202)
■ Discuss the anatomy of the thyroid gland, and produced by glands.
the chemistry and physiological function of its ■ State the location and function of the pineal What's New
hormones. gland and the thymus gland. Pancreatic Islet Cell Transplants (p. 197)
■ Discuss the function of parathyroid hormone.

185
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Physiology, Fifth Edition

10.1 Endocrine Glands the nervous system, the endocrine system is intimately in-
volved in homeostasis.
The endocrine system consists of glands and tissues that secrete Hormones are chemical signals that affect the behavior of
hormones. This chapter will give many examples of the close other glands or tissues. Hormones influence the metabolism
association between the endocrine and nervous systems. Like of cells, the growth and development of body parts, and
homeostasis. Endocrine glands are ductless; they secrete their
Figure 10.1 The endocrine system. Anatomical location of hormones into tissue fluid. From there, they diffuse into the
major endocrine glands in the body. The hypothalamus and bloodstream for distribution throughout the body. Endocrine
pituitary gland are in the brain, the thyroid and parathyroids are in glands can be contrasted with exocrine glands, which have
the neck, and the adrenal glands and pancreas are in the pelvic ducts and secrete their products into these ducts. For example,
cavity. The gonads include the ovaries in females, located in the the salivary glands send saliva into the mouth by way of the
pelvic cavity, and the testes in males, located outside this cavity in salivary ducts.
the scrotum. Also shown are the pineal gland, located in the brain, Figure 10.1 depicts the locations of the major endocrine
and the thymus gland, which lies within the thoracic cavity. glands in the body, and Table 10.1 lists the hormones they re-
lease. Each type of hormone has a different composition.
Even so, hormones can be categorized as either peptides
(which include proteins, glycoproteins, and modified amino
acids) or steroids. Protein hormones, such as insulin, must be
hypothalamus pineal gland administered by injection. If these hormones were taken
pituitary gland orally, they would be acted on by digestive enzymes. Steroid
(hypophysis)
hormones, such as those in birth control pills, can be taken
orally because they can pass through the plasma membrane
without prior digestion.

thyroid gland Hormones and Homeostasis

The effect of hormones is usually controlled in two ways: (1)
parathyroid gland
Negative feedback opposes their release, and (2) antagonistic
hormones oppose each other’s actions. Notice in Table 10.1
thymus gland
that several hormones directly affect the blood glucose, cal-
cium, and sodium levels. Other hormones are involved in the
function of various organs, including the reproductive organs.
Some hormones or their effects are controlled by a nega-
tive feedback system. The result is that the activity of the hor-
mone is maintained within normal limits. The negative feed-
adrenal gland back system can be sensitive to either a resulting condition or
to the blood level of a hormone. For example, when the blood
pancreas glucose level rises, the pancreas secretes insulin, which causes
the liver to store glucose and the cells to take it up. When
blood glucose lowers, the secretion of insulin is inhibited,
ovary and the pancreas stops producing insulin. On the other hand,
when the blood level of thyroid hormones rises, the anterior
pituitary stops secreting thyroid-stimulating hormones. These
examples illustrate regulation by negative feedback.
The actions of a hormone can also be controlled by the
presence of an antagonistic hormone. The effect of insulin, for
example, is offset by the production of glucagon by the pan-
creas. Insulin lowers the blood glucose level, while glucagon
raises it. Also, the thyroid lowers the blood calcium level, but
the parathyroids raise the blood calcium level. In subsequent
testis
sections of this chapter, we will point out other instances in
which hormones work opposite to one another, and thereby
bring about the regulation of a substance in the blood.

186 Part III Integration and Coordination

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Physiology, Fifth Edition

Table 10.1 Principal Endocrine Glands and Hormones

Endocrine Hormone Chemical Target Chief Function(s)
Gland Released Class Tissues/Organs of Hormone

Hypothalamus Hypothalamic-releasing and Peptide Anterior pituitary Regulate anterior pituitary hormones
-inhibiting hormones
Pituitary gland
Posterior pituitary Antidiuretic (ADH) Peptide Kidneys Stimulates water reabsorption by
kidneys
Oxytocin Peptide Uterus, mammary Stimulates uterine muscle contraction,
glands release of milk by mammary glands
Anterior pituitary Thyroid-stimulating (TSH) Glycoprotein Thyroid Stimulates thyroid
Adrenocorticotropic (ACTH) Peptide Adrenal cortex Stimulates adrenal cortex
Gonadotropic Glycoprotein Gonads Egg and sperm production;
sex hormone production
Prolactin (PRL) Protein Mammary glands Milk production
Growth (GH) Protein Soft tissues, bones Cell division, protein synthesis, and
bone growth
Melanocyte-stimulating (MSH) Peptide Melanocytes in skin Unknown function in humans;
regulates skin color in lower
vertebrates
Thyroid Thyroxine (T4) and Iodinated All tissues Increases metabolic rate; regulates
triiodothyronine (T3) amino acid growth and development
Calcitonin Peptide Bones, kidneys, Lowers blood calcium level
intestine
Parathyroids Parathyroid (PTH) Peptide Bones, kidneys, Raises blood calcium level
intestine
Adrenal gland
Adrenal cortex Glucocorticoids (cortisol) Steroid All tissues Raise blood glucose level; stimulate
breakdown of protein
Mineralocorticoids (aldosterone) Steroid Kidneys Reabsorb sodium and excrete
potassium
Sex hormones Steroid Gonads, skin, Stimulate reproductive organs and
muscles, bones bring about sex characteristics

Adrenal medulla Epinephrine and norepinephrine Modified Cardiac and other Released in emergency situations;
amino acid muscles raise blood glucose level
Pancreas Insulin Protein Liver, muscles, Lowers blood glucose level;
adipose tissue promotes formation of glycogen
Glucagon Protein Liver, muscles, Raises blood glucose level
adipose tissue
Gonads
Testes Androgens (testosterone) Steroid Gonads, skin, Stimulate male sex characteristics
muscles, bones
Ovaries Estrogens and progesterone Steroid Gonads, skin, Stimulate female sex characteristics
muscles, bones
Thymus Thymosins Peptide T lymphocytes Stimulate production and maturation
of T lymphocytes
Pineal gland Melatonin Modified Brain Controls circadian and circannual
amino acid rhythms; possibly involved in
maturation of sexual organs

Chapter 10 The Endocrine System 187

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Physiology, Fifth Edition

10.2 Hypothalamus and pituitary (Fig. 10.2, right). The hypothalamus controls the an-
terior pituitary by producing hypothalamic-releasing hor-
Pituitary Gland mones and hypothalamic-inhibiting hormones. For exam-
ple, there is a thyrotropin-releasing hormone (TRH) and a
The hypothalamus regulates the internal environment. For
prolactin-inhibiting hormone (PIH). TRH stimulates the an-
example, through the autonomic system, it helps control
terior pituitary to secrete thyroid-stimulating hormone, and
heartbeat, body temperature, and water balance (by creating
PIH inhibits the pituitary from secreting prolactin.
thirst). The hypothalamus also controls the glandular secre-
tions of the pituitary gland (hypophysis). The pituitary, a
small gland about 1 cm in diameter, is connected to the Hormones That Affect Other Glands
hypothalamus by a stalklike structure. The pituitary has two
Three of the hormones produced by the anterior pituitary
portions: the posterior pituitary (neurohypophysis) and the
have an effect on other glands: Thyroid-stimulating hor-
anterior pituitary (adrenohypophysis).
mone (TSH) stimulates the thyroid to produce the thyroid
hormones; adrenocorticotropic hormone (ACTH) stimu-
Posterior Pituitary lates the adrenal cortex to produce its hormones; and go-
nadotropic hormones stimulate the gonads—the testes in
Neurons in the hypothalamus called neurosecretory cells
males and the ovaries in females—to produce gametes and
produce the hormones antidiuretic hormone (ADH) and oxy-
sex hormones. The hypothalamus, the anterior pituitary, and
tocin (Fig. 10.2, left). These hormones pass through axons
other glands controlled by the anterior pituitary are all in-
into the posterior pituitary where they are stored in axon
volved in self-regulating negative feedback mechanisms that
endings.
maintain stable conditions. In each instance, the blood level
of the last hormone in the sequence exerts negative feedback
Antidiuretic Hormone and Oxytocin control over the secretion of the first two hormones:
Certain neurons in the hypothalamus are sensitive to the
water–salt balance of the blood. When these cells determine Hypothalamus
that the blood is too concentrated, antidiuretic hormone
(ADH) is released from the posterior pituitary. Upon reaching releasing hormone
the kidneys, ADH causes more water to be reabsorbed into (hormone 1)
kidney capillaries. As the blood becomes dilute, ADH is no
longer released. This is an example of control by negative Feedback inhibits
release of hormone 1. Anterior pituitary
feedback because the effect of the hormone (to dilute blood)
acts to shut down the release of the hormone. Negative feed-
back maintains stable conditions and homeostasis. stimulating hormone
(hormone 2)
Inability to produce ADH causes diabetes insipidus (wa- Feedback inhibits
tery urine), in which a person produces copious amounts of release of hormone 2.
urine with a resultant loss of ions from the blood. The condi- Target gland
tion can be corrected by the administration of ADH.
Oxytocin, the other hormone made in the hypothala- target gland hormone
mus, causes uterine contraction during childbirth and milk (hormone 3)
letdown when a baby is nursing. The more the uterus con-
tracts during labor, the more nerve impulses reach the hypo-
Effects of Other Hormones
thalamus, causing oxytocin to be released. Similarly, the more
a baby suckles, the more oxytocin is released. In both in- Other hormones produced by the anterior pituitary do not
stances, the release of oxytocin from the posterior pituitary is affect other endocrine glands. Prolactin (PRL) is produced in
controlled by positive feedback—that is, the stimulus con- quantity after childbirth. It causes the mammary glands in
tinues to bring about an effect that ever increases in intensity. the breasts to develop and produce milk. It also plays a role
Positive feedback is not a way to maintain stable conditions in carbohydrate and fat metabolism.
and homeostasis. Growth hormone (GH), or somatotropic hormone,
stimulates protein synthesis within cartilage, bone, and mus-
cle. It stimulates the rate at which amino acids enter cells and
Anterior Pituitary
protein synthesis occurs. It also promotes fat metabolism as
A portal system, consisting of two capillary systems connected opposed to glucose metabolism.
by a vein, lies between the hypothalamus and the anterior

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Human Anatomy & Coordination Companies, 2004
Physiology, Fifth Edition

hypothalamus
• Neurosecretory
cells produce ADH
and oxytocin. • Neurosecretory cells produce
hypothalamic-releasing and
hypothalamic-inhibiting
hormones.

• These hormones move

down axons to axon endings.

portal • These hormones are

system secreted into a portal system.

• Each type of hypothalamic

hormone either stimulates or
inhibits production and secretion
of an anterior pituitary hormone.
• When appropriate, ADH and
oxytocin are secreted from • The anterior pituitary secretes
axon endings into the bloodstream. its hormones into the bloodstream.

posterior pituitary anterior pituitary

antidiuretic gonadotropic
hormone (ADH) hormones

kidney tubules
ovaries, testes

oxytocin growth
hormone (GH)
oxytocin prolactin (PRL)
adrenocortico-
thyroid- tropic hormone
stimulating (ACTH)
hormone (TSH)

smooth muscle
in uterus mammary
mammary bones, tissues
glands
glands
adrenal cortex
thyroid

Figure 10.2 The hypothalamus and the pituitary. Left: The hypothalamus produces two hormones, ADH and oxytocin, which are stored
and secreted by the posterior pituitary. Right: The hypothalamus controls the secretions of the anterior pituitary, and the anterior pituitary
controls the secretions of the thyroid, adrenal cortex, and gonads, which are also endocrine glands. It also secretes growth hormone and
prolactin.

Chapter 10 The Endocrine System 189

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Physiology, Fifth Edition

Effects of Growth Hormone Figure 10.3 Effect of growth hormone. a. The amount of growth hormone produced by the
anterior pituitary during childhood affects the height of an individual. Plentiful growth hormone
The amount of GH produced by the
produces very tall basketball players. b. Too much growth hormone can lead to giantism, while an
anterior pituitary affects the height
insufficient amount results in limited stature and even pituitary dwarfism.
of the individual. The quantity of
GH produced is greatest during
childhood and adolescence, when
most body growth is occurring (Fig.
10.3a). If too little GH is produced
during childhood, the individual
has pituitary dwarfism, character-
ized by perfect proportions but small
stature. If too much GH is secreted, a
person can become a giant (Fig.
10.3b). Giants usually have poor
health, primarily because GH has a
secondary effect on the blood sugar
level, promoting an illness called
diabetes mellitus (see page 197).
On occasion, GH is overpro-
duced in the adult, and a condition
called acromegaly results. Because
long bone growth is no longer possi-
ble in adults, only the feet, hands,
and face (particularly the chin, nose,
and eyebrow ridges) can respond, and
these portions of the body become
overly large (Fig. 10.4).

a. b.

Figure 10.4 Acromegaly. Acromegaly is caused by overproduction of GH in the adult. It is characterized by enlargement of the bones in
the face, the fingers, and the toes as a person ages.

Age 9 Age 16 Age 33 Age 52

190 Part III Integration and Coordination

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Physiology, Fifth Edition

10.3 Thyroid and Parathyroid body to metabolize at a faster rate. More glucose is broken
down, and more energy is utilized.
Glands If the thyroid fails to develop properly, a condition called
cretinism results (Fig. 10.6). Individuals with this condition are
The thyroid gland is a large gland located in the neck, where
short and stocky and have had extreme hypothyroidism (under-
it is attached to the trachea just below the larynx (see Fig.
secretion of thyroid hormone) since infancy or childhood. Thy-
10.1). The parathyroid glands are embedded in the posterior
roid hormone therapy can initiate growth, but unless treatment
surface of the thyroid gland.
is begun within the first two months of life, mental retardation
results. The occurrence of hypothyroidism in adults produces
Thyroid Gland the condition known as myxedema, which is characterized by
The thyroid gland is composed of a large number of follicles, lethargy, weight gain, loss of hair, slower pulse rate, lowered
each a small spherical structure made of thyroid cells filled body temperature, and thickness and puffiness of the skin. The
with triiodothyronine (T3), which contains three iodine administration of adequate doses of thyroid hormones restores
atoms, and thyroxine (T4), which contains four iodine atoms. normal function and appearance.
In the case of hyperthyroidism (oversecretion of thyroid
Effects of Thyroid Hormones hormone), as seen in Graves disease, the thyroid gland is over-
active, and a goiter forms. This type of goiter is called exoph-
To produce triiodothyronine and thyroxine, the thyroid gland
thalmic goiter. The eyes protrude because of edema in eye
actively acquires iodine. The concentration of iodine in the
socket tissues and swelling of the muscles that move the eyes.
thyroid gland can increase to as much as 25 times that of the
The patient usually becomes hyperactive, nervous, and irritable,
blood. If iodine is lacking in the diet, the thyroid gland is
and suffers from insomnia. Removal or destruction of a portion
unable to produce the thyroid hormones. In response to
of the thyroid by means of radioactive iodine is sometimes ef-
constant stimulation by the anterior pituitary, the thyroid
fective in curing the condition. Hyperthyroidism can also be
enlarges, resulting in a simple goiter (Fig. 10.5). Some years
caused by a thyroid tumor, which is usually detected as a lump
ago, it was discovered that the use of iodized salt allows the
during physical examination. Again, the treatment is surgery in
thyroid to produce the thyroid hormones, and therefore helps
combination with administration of radioactive iodine. The
prevent simple goiter.
prognosis for most patients is excellent.
Thyroid hormones increase the metabolic rate. They do
not have a target organ; instead, they stimulate all cells of the

Figure 10.5 Simple goiter. An enlarged thyroid gland is often Figure 10.6 Cretinism. Individuals who have hypothyroidism
caused by a lack of iodine in the diet. Without iodine, the thyroid is since infancy or childhood do not grow and develop as others do.
unable to produce its hormones, and continued anterior pituitary Unless medical treatment is begun, the body is short and stocky;
stimulation causes the gland to enlarge. mental retardation is also likely.

Chapter 10 The Endocrine System 191

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Physiology, Fifth Edition

Calcitonin Parathyroid Glands

2!
Calcium (Ca ) plays a significant role in both nervous Parathyroid hormone (PTH), the hormone produced by the
conduction and muscle contraction. It is also necessary for parathyroid glands, causes the blood phosphate (HPO42")
coagulation (clotting) of blood. The blood calcium level is level to decrease and the blood calcium (Ca2!) level to in-
regulated in part by calcitonin, a hormone secreted by the crease. The antagonistic actions of calcitonin, from the thy-
thyroid gland when the blood calcium level rises (Fig. roid gland, and parathyroid hormone, from the parathyroid
10.7). The primary effect of calcitonin is to bring about glands, maintain the blood calcium level within normal
the deposit of calcium in the bones. It does this by tem- limits.
porarily reducing the activity and number of osteoclasts. Note in Figure 10.7 that after a low blood calcium level
When the blood calcium lowers to normal, the release of stimulates the release of PTH, it promotes release of calcium
calcitonin by the thyroid is inhibited, but a low calcium from the bones. (It does this by promoting the activity of os-
level stimulates the release of parathyroid hormone (PTH) teoclasts.) PTH promotes the reabsorption of calcium by the
by the parathyroid glands. kidneys, where it also activates vitamin D. Vitamin D, in turn,
stimulates the absorption of calcium
from the intestine. These effects bring the
blood calcium level back to the normal
calcitonin
range so that the parathyroid glands no
longer secrete PTH.
Many years ago, the four parathy-
roid glands were sometimes mistakenly
removed during thyroid surgery because
of their size and location in the thyroid.
When insufficient parathyroid hormone
Thyroid gland Bones production leads to a dramatic drop in
secretes calcitonin take up Ca2+
into blood.
the blood calcium level, tetany results.
from blood.
In tetany, the body shakes from contin-
uous muscle contraction. This effect is
Blood Ca2+ lowers. brought about by increased excitability
of the nerves, which initiate nerve im-
pulses spontaneously and without rest.
hig
hb
loo
dC
a 2+
Homeostasis
normal blood Ca2+
low
blo
od
Ca 2+

Figure 10.7 Regulation of blood

Blood Ca2+ rises.
Parathyroid glands calcium level. Top: When the blood calcium
release PTH (Ca2!) level is high, the thyroid gland
into blood. secretes calcitonin. Calcitonin promotes the
activated uptake of Ca2! by the bones, and therefore
vitamin D the blood Ca2! level returns to normal.
parathyroid Bottom: When the blood Ca2! level is low,
hormone (PTH) the parathyroid glands release parathyroid
hormone (PTH). PTH causes the bones to
release Ca2!. It also causes the kidneys to
Intestines Bones reabsorb Ca2! and activate vitamin D;
absorb Ca2+ Kidneys release Ca2+ thereafter, the intestines absorb Ca2!.
from digestive reabsorb Ca2+ into blood.
tract. from kidney Therefore, the blood Ca2! level returns to
tubules. normal.

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Physiology, Fifth Edition

10.4 Adrenal Glands reacts to an emergency situation. The effects of these hor-
mones provide a short-term response to stress.
The adrenal glands sit atop the kidneys (see Fig. 10.1). Each
adrenal gland consists of an inner portion called the adrenal
Adrenal Cortex
medulla and an outer portion called the adrenal cortex.
These portions, like the anterior pituitary and the posterior In contrast, the hormones produced by the adrenal cortex
pituitary, have no physiological connection with one another. provide a long-term response to stress (Fig. 10.8). The two
The adrenal medulla is under nervous control, and the ad- major types of hormones produced by the adrenal cortex are
renal cortex is under the control of ACTH, an anterior pitu- the mineralocorticoids and the glucocorticoids. The miner-
itary hormone. Stress of all types, including emotional and alocorticoids regulate salt and water balance, leading to in-
physical trauma, prompts the hypothalamus to stimulate creases in blood volume and blood pressure. The glucocorti-
the adrenal glands (Fig. 10.8). coids regulate carbohydrate, protein, and fat metabolism,
leading to an increase in blood glucose level. Cortisone, the
medication often administered for inflammation of joints, is
Adrenal Medulla a glucocorticoid.
The hypothalamus initiates nerve impulses that travel by way The adrenal cortex also secretes a small amount of male
of the brain stem, spinal cord, and sympathetic nerve fibers to sex hormones and a small amount of female sex hormones in
the adrenal medulla, which then secretes its hormones. both sexes. That is, in the male, both male and female sex hor-
Epinephrine (adrenaline) and norepinephrine (nor- mones are produced by the adrenal cortex, and in the female,
adrenaline) produced by the adrenal medulla rapidly bring both male and female sex hormones are also produced by the
about all the body changes that occur when an individual adrenal cortex.

stress

path of nerve
impulses hypothalamus
Neurosecretory cells produce
hypothalamic-releasing
hormone.

spinal cord neuron Anterior pituitary

(cross section) cell body secretes ACTH.

sympathetic
Stress Response: Long Term
fibers
Glucocorticoids
epinephrine
Protein and fat metabolism occur
norepinephrine
instead of glucose breakdown.

Inflammation is reduced;
immune cells are suppressed.
ACTH
Stress Response: Short Term
Mineralocorticoids
Heartbeat and blood
pressure increase. Sodium ions and water are
adrenal medulla adrenal cortex reabsorbed by kidney.
Blood glucose level rises.
Blood volume and pressure
Muscles become energized. increase.

Figure 10.8 Adrenal glands. Both the adrenal medulla and the adrenal cortex are under the control of the hypothalamus when they
help us respond to stress. Left: The adrenal medulla provides a rapid, but short-term, stress response. Right: The adrenal cortex provides a
slower, but long-term, stress response.

Chapter 10 The Endocrine System 193

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Physiology, Fifth Edition

Glucocorticoids effect of this system, called the renin-angiotensin-aldosterone

system, is to raise blood pressure in two ways: Angiotensin II
Cortisol is a biologically significant glucocorticoid produced constricts arterioles, and aldosterone causes the kidneys to re-
by the adrenal cortex. Cortisol raises the blood glucose level in absorb sodium. When the blood sodium level rises, water is
at least two ways: (1) It promotes the breakdown of muscle reabsorbed in part because the hypothalamus secretes ADH
proteins to amino acids, which are taken up by the liver from (see page 188). Reabsorption means that water enters kidney
the bloodstream. The liver then breaks down these excess capillaries and thus the blood. Then blood pressure increases
amino acids to glucose, which enters the blood. (2) Cortisol to normal.
promotes the metabolism of fatty acids rather than carbohy- There is an antagonistic hormone to aldosterone, as you
drates, and this spares glucose for the brain. might suspect. When the atria of the heart are stretched due to
Cortisol also counteracts the inflammatory response that increased blood volume, cardiac cells release a hormone
leads to the pain and swelling of joints in arthritis and bursitis. called atrial natriuretic hormone (ANH), which inhibits the
The administration of cortisol aids these conditions because it secretion of aldosterone from the adrenal cortex. The effect of
reduces inflammation. Very high levels of glucocorticoids in ANH is the excretion of sodium—that is, natriuresis. When
the blood can suppress the body’s defense system, including sodium is excreted, so is water, and therefore blood pressure
the inflammatory response that occurs at infection sites. Corti- lowers to normal.
sone and other glucocorticoids can relieve swelling and pain
from inflammation, but by suppressing pain and immunity,
they can also make a person highly sus-
ceptible to injury and infection. atrial natriuretic
hormone (ANH)

Mineralocorticoids
Aldosterone is the most important of the
mineralocorticoids. Aldosterone prima-
rily targets the kidney where it promotes
Heart secretes Kidneys excrete
renal absorption of sodium (Na!) and re- atrial natriuretic Na+ and water
nal excretion of potassium (K!). hormone (ANH) in urine.
The secretion of mineralocorticoids into blood.
is not controlled by the anterior pitu-
itary. When the blood sodium level and
therefore the blood pressure are low, the
kidneys secrete renin (Fig. 10.9). Renin
is an enzyme that converts the plasma high
bloo
protein angiotensinogen to angiotensin dN
a+
I, which is changed to angiotensin II by Homeostasis
a converting enzyme found in lung normal blood pressure
low
capillaries. Angiotensin II stimulates the bloo
dN
adrenal cortex to release aldosterone. The a+

Figure 10.9 Regulation of blood

pressure and volume. Bottom: When the
blood sodium (Na!) level is low, a low blood
pressure causes the kidneys to secrete
renin. Renin leads to the secretion of Kidneys reabsorb Kidneys secrete
Na+ and water renin into blood.
aldosterone from the adrenal cortex. from kidney tubules.
Aldosterone causes the kidneys to reabsorb
Na!, and water follows, so that blood
volume and pressure return to normal. renin
Top: When the blood Na! is high, a high aldosterone
blood volume causes the heart to secrete
atrial natriuretic hormone (ANH). ANH
causes the kidneys to excrete Na!, and angiotensin
Adrenal cortex
water follows. The blood volume and secretes aldosterone I and II
pressure return to normal. into blood.

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Physiology, Fifth Edition

Malfunction of the Adrenal Cortex lead to death. The lack of aldosterone results in a loss of
sodium and water, the development of low blood pressure,
Malfunction of the adrenal cortex can lead to a syndrome, a and possibly severe dehydration. Left untreated, Addison dis-
set of symptoms that occur together. The syndromes com- ease can be fatal.
monly associated with the adrenal cortex are Addison disease When the level of adrenal cortex hormones is high due to
and Cushing syndrome. hypersecretion, a person develops Cushing syndrome (Fig.
10.11). The excess cortisol results in a tendency toward diabetes
Addison Disease and Cushing Syndrome mellitus as muscle protein is metabolized and subcutaneous fat
When the level of adrenal cortex hormones is low due to hy- is deposited in the midsection. The trunk is obese, while the
posecretion, a person develops Addison disease. The pres- arms and legs remain a normal size. An excess of aldosterone
ence of excessive but ineffective ACTH causes a bronzing of and reabsorption of sodium and water by the kidneys leads to a
the skin because ACTH can lead to a buildup of melanin basic blood pH and hypertension. The face is moon-shaped due
(Fig. 10.10). Without cortisol, glucose cannot be replenished to edema. Masculinization may occur in women because of ex-
when a stressful situation arises. Even a mild infection can cess adrenal male sex hormones.

a. b.

Figure 10.10 Addison disease. Addison disease is characterized by a peculiar bronzing of the skin, particularly noticeable in these
light-skinned individuals. Note the color of (a) the face and (b) the hands compared to the hand of an individual without the disease.

Figure 10.11 Cushing syndrome.

Cushing syndrome results from
hypersecretion of adrenal cortex hormones.
a. Patient first diagnosed with Cushing
syndrome. b. Four months later, after
therapy. a. b.

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Physiology, Fifth Edition

10.5 Pancreas and muscle cells, glucose is then stored as glycogen. In muscle
cells, the glucose supplies energy for muscle contraction, and
The pancreas is a long organ that lies transversely in the ab- in fat cells, glucose enters the metabolic pool and thereby sup-
domen between the kidneys and near the duodenum of the plies glycerol for the formation of fat. In these ways, insulin
small intestine. It is composed of two types of tissue. Exocrine lowers the blood glucose level. As discussed in the What’s
tissue produces and secretes digestive juices that go by way of New reading on page 197, individuals who do not produce
ducts to the small intestine. Endocrine tissue, called the pan- insulin have a condition called diabetes mellitus type I.
creatic islets (islets of Langerhans), produces and secretes the Glucagon is secreted from the pancreas, usually between
hormones insulin and glucagon directly into the blood (Fig. meals, when the blood glucose level is low. The major target
10.12). tissues of glucagon are the liver and adipose tissue. Glucagon
The two antagonistic hormones insulin and glucagon, stimulates the liver to break down glycogen to glucose and to
both produced by the pancreas, help maintain the normal use fat and protein in preference to glucose as energy sources.
level of glucose in the blood. Insulin is secreted when the Adipose tissue cells break down fat to glycerol and fatty acids.
blood glucose level is high, which usually occurs just after eat- The liver takes these up and uses them as substrates for glu-
ing. Insulin stimulates the uptake of glucose by cells, espe- cose formation. In these ways, glucagon raises the blood glu-
cially liver cells, muscle cells, and adipose tissue cells. In liver cose level.

insulin

Liver stores glucose from

blood as glycogen.
Pancreas secretes
insulin into blood.

Muscle cells store

after glycogen and build
eating protein.

Adipose tissue uses

glucose from blood
hig to form fat.
hb
loo
dg
luc
ose

Homeostasis
normal blood glucose

low
blo
od
glu
cos
e Figure 10.12 Regulation of blood
glucose level. Top: When the blood
glucose level is high, the pancreas
in secretes insulin. Insulin promotes the
between storage of glucose as glycogen in the
Liver breaks down eating liver and muscles and the use of glucose
glycogen to glucose.
to form fat in adipose tissue. Therefore,
Glucose enters blood.
insulin lowers the blood glucose level.
Bottom: When the blood glucose level is
low, the pancreas secretes glucagon.
Glucagon acts opposite to insulin;
glucagon therefore, glucagon raises the blood
Adipose tissue Pancreas secretes
breaks down fat. glucagon into blood. glucose level to normal.

196 Part III Integration and Coordination

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Physiology, Fifth Edition

Pancreatic Islet Cell Transplants

“I can remember getting sick with the flu just before I was diag- clinical studies, islet cells have been successfully implanted into
nosed. I was eleven, and I was sick enough to miss two or three human volunteers, who were then able to stop insulin injections.
days of school. Then I just never got my strength back. I ate and It is estimated that 700,000 islets will be needed to produce
drank constantly because I was thirsty and hungry all the time. I enough insulin for an adult. Several donor pancreases are needed
was always in the bathroom. It was so embarrassing. I started wet- to harvest sufficient islet cells for a single transplant. If an animal
ting the bed—can you imagine, at age 11? I fell asleep in school, cell source could be used, unlimited islet cells would be available.
and the teacher could barely get me to wake up. That’s when my Heart valves from pigs have been used for decades, and insulin for
doctor diagnosed my diabetes for the first time.” injection into humans was first isolated from pigs. Tissue engi-
The patient, age 25, is a typical type I, juvenile-onset or neers are now experimenting with islet cells from pigs. These islet
insulin-dependent diabetic. Her symptoms are classic for insulin- cells have been isolated and surrounded by a semipermeable
dependent diabetes mellitus (IDDM) (see page 198). plastic membrane, a process called microencapsulation. These
In insulin-dependent diabetes, the insulin-producing islet capsules are so small that they can be placed into the abdomen,
cells of the pancreas have been destroyed. Researchers think this is where they will float freely and produce insulin as needed (Fig.
due to a malfunction of the immune system that causes the 10A). The membrane of the capsule contains pores large enough
body’s own immune cells to target the pancreas. Thus, insulin- to allow oxygen and nutrients to flow in and wastes and insulin to
dependent diabetes is considered an autoimmune disease. As the flow out by diffusion. But the membrane prevents immune cells
name suggests, insulin must be taken by injection. The diabetic from coming into contact with the enclosed pancreatic cells. Un-
patient’s life then revolves around two to three daily insulin in- less immune cells actually come in contact with transplanted
jections or monitoring by an insulin pump device that injects in- cells, they cannot destroy them. Therefore, the patient does not
sulin automatically. Four or more daily blood tests are used to need to take harsh antirejection drugs, and the immune system
check blood glucose levels, and the patient must also monitor can function normally to suppress infection and cancer. Re-
diet, activity level, exercise, and stress. searchers are optimistic that prepared microencapsulated islet
“My insulin pump saves me from those three-a-day shots, cells could soon be available for clinical trials.
but boy, do I hate finger sticks to test my blood,” the patient says
with a wistful smile. “I know how carefully I have to man-
age this disease. Diabetics lose their sight, or go into kid-
ney failure, or wind up having an early heart attack or
stroke. I wish I could be placed on a transplant list for a
pancreas, but everybody wants a pancreas. There aren’t
enough human donors to go around.”
Pancreatic transplantation has been available to
IDDM sufferers since 1966, but it suffers from the same
limitations of all transplant technology. Transplanting an
entire organ is major surgery, and there is always a shortage
of available donors. Strong drugs must be taken for the rest
of the patient’s life in order to suppress the immune sys-
tem. These antirejection drugs can have toxic effects on
normal body cells. Moreover, with a weakened immune
system, the patient has an increased risk of developing life-
threatening infections or cancer.
The technique of pancreatic islet cell transplantation
seems to hold promise for solving the problems of the
traditional pancreas transplant. The islet cells are first iso-
lated from a donor pancreas. The cells are then directly
injected through the hepatic portal vein into the liver,
where they form colonies and begin to produce insulin. Figure 10A Encapsulated insulin-producing pancreatic islet cells from pigs
This technique is much simpler than whole-pancreas can be transplanted into patients without the need for immune system-
transplantation and does not involve major surgery. In suppressing drugs.

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Physiology, Fifth Edition

Diabetes Mellitus 10.6 Other Endocrine Glands

Diabetes mellitus is a fairly common hormonal disease in The body has a number of other endocrine glands, including
which liver cells, and indeed all body cells, are unable to take the gonads (testes in males and the ovaries in females). Other
up and/or metabolize glucose. Therefore, the blood glucose lesser-known glands, such as the thymus gland and the pineal
level is elevated, called hyperglycemia, and the person be- gland, also produce hormones. Some tissues within organs pro-
comes extremely hungry, called polyphagia. As the blood duce hormones and/or growth factors. Individual body cells
glucose level rises, glucose and water are excreted in excess, produce prostaglandins.
called glycosuria and polyuria, respectively. The loss of water
in this way causes the diabetic to be extremely thirsty, called
polydipsia. Since glucose is not being metabolized, the body Testes and Ovaries
turns to the breakdown of protein and fat for energy. The testes are located in the scrotum, and the ovaries are
We now know that diabetes mellitus exists in two forms. located in the pelvic cavity. The testes produce androgens
In type I, more often called insulin-dependent diabetes mel- (e.g., testosterone), which are the male sex hormones, and
litus (IDDM), the pancreas is not producing insulin. This the ovaries produce estrogens and progesterone, the female
condition is believed to be brought on, at least in part, by ex- sex hormones. The hypothalamus and the pituitary gland
posure to an environmental agent, most likely a virus, whose control the hormonal secretions of these organs in the man-
presence causes immune cells to destroy the pancreatic islets. ner previously described on page 188.
The body turns to the metabolism of fat, which leads to the
buildup of ketones in the blood, called ketonuria, and in turn
to acidosis (acid blood), which can lead to coma and death. Androgens
As a result, the individual must have daily insulin injections. Puberty is the time of life when sexual maturation occurs.
These injections control the diabetic symptoms but can still Greatly increased testosterone secretion during puberty stim-
cause inconveniences, because either an overdose of insulin ulates the growth of the penis and the testes. Testosterone
or missing a meal can bring on the symptoms of hypo- also brings about and maintains the male secondary sex char-
glycemia (low blood sugar). These symptoms include perspi- acteristics that develop during puberty, including the growth
ration, pale skin, shallow breathing, and anxiety. The cure is of a beard, axillary (underarm) hair, and pubic hair. It
quite simple: Immediate ingestion of a sugar cube or fruit prompts the larynx and the vocal cords to enlarge, causing
juice can very quickly counteract hypoglycemia. the voice to change. It is partially responsible for the muscu-
Of the 16 million people who now have diabetes in the lar strength of males, and this is why some athletes take sup-
United States, most have type II, more often called noninsulin- plemental amounts of anabolic steroids, which are either
dependent diabetes (NIDDM). This type of diabetes mellitus testosterone or related chemicals. The contraindications of
usually occurs in people of any age who tend to be obese— taking anabolic steroids are discussed in the Medical Focus
adipose tissue produces a substance that interferes with the on page 199. Testosterone also stimulates oil and sweat
transport of glucose into cells. The amount of insulin in the glands in the skin; therefore, it is largely responsible for acne
blood is normal or elevated, but the insulin receptors on and body odor. Another side effect of testosterone is bald-
the cells do not respond to it. It is possible to prevent, or at ness. Genes for baldness are probably inherited by both
least control, type II diabetes by adhering to a low-fat, low- sexes, but baldness is seen more often in males because of the
sugar diet and exercising regularly. If this fails, oral drugs that presence of testosterone.
stimulate the pancreas to secrete more insulin and enhance
the metabolism of glucose in the liver and muscle cells are
Estrogen and Progesterone
available. It’s projected that as many as 7 million Americans
may have type II diabetes without being aware of it. Yet, the The female sex hormones, estrogens and progesterone, have
effects of untreated type II diabetes are as serious as those of many effects on the body. In particular, estrogens secreted
type I diabetes. during puberty stimulate the growth of the uterus and the
Long-term complications of both types of diabetes are vagina. Estrogen is necessary for egg maturation and is largely
blindness, kidney disease, and circulatory disorders, includ- responsible for the secondary sex characteristics in females,
ing atherosclerosis, heart disease, stroke, and reduced circula- including female body hair and fat distribution. In general, fe-
tion. The latter can lead to gangrene in the arms and legs. males have a more rounded appearance than males because
Pregnancy carries an increased risk of diabetic coma, and the of a greater accumulation of fat beneath the skin. Also, the
child of a diabetic is somewhat more likely to be stillborn or pelvic girdle is wider in females than in males, resulting in a
to die shortly after birth. However, these complications of di- larger pelvic cavity. Both estrogen and progesterone are re-
abetes are not expected to appear if the mother’s blood glu- quired for breast development and for regulation of the uter-
cose level is carefully regulated and kept within normal limits ine cycle, which includes monthly menstruation (discharge of
during the pregnancy. blood and mucosal tissues from the uterus).

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Physiology, Fifth Edition

Side Effects of Anabolic Steroids

Anabolic steroids are synthetic forms of the male sex hormone retain fluid, which results in increased blood pressure. Users then try
testosterone. Taking doses 10 to 100 times the amount prescribed by to get rid of “steroid bloat” by taking large doses of diuretics. A
doctors for various illnesses promotes larger muscles when the per- young California weight lifter had a fatal heart attack after using
son also exercises. Trainers may have been the first to acquire ana- steroids, and the postmortem showed a lack of electrolytes, salts
bolic steroids for weight lifters, bodybuilders, and other athletes, that help regulate the heart. Finally, steroid abuse has psychological
such as professional football players. However, being a steroid user effects, including depression, hostility, aggression, and eating disor-
can have serious detrimental effects. Men often experience decreased ders. Unfortunately, these drugs make a person feel invincible.
sperm counts and decreased sexual desire due to atrophy of the tes- One abuser even had his friend videotape him as he drove his car
ticles. Some develop an enlarged prostate gland or grow breasts. On at 40 miles an hour into a tree!
the other hand, women can develop male sexual characteristics. The many harmful effects of anabolic steroids are given in
They grow hair on their chests and faces, and lose hair from their Figure 10B. The Federal Food and Drug Administration now bans
heads; many experience abnormal enlargement of the clitoris. Some most steroids, and steroid use has also been banned by the
cease ovulating or menstruating, sometimes permanently. National Collegiate Athletic Association (NCAA), the National
Some researchers predict that two or three months of high- Football League (NFL), and the International Olympic Commit-
dosage use of anabolic steroids as a teen can cause death by age tee (IOC). Of great concern is the increased use of steroids by
30 or 40. Steroids have even been linked to heart disease in both teenagers wishing to build bulk quickly, possibly due to society’s
sexes and implicated in the deaths of young athletes from liver can- emphasis on physical appearance and adolescents’ need to feel
cer and one type of kidney tumor. Steroids can cause the body to better about how they look.

balding in men and women; 'roid mania– hostility and

hair on face and chest aggression; delusions and
in women hallucinations; depression
upon withdrawal
beard and deepening of voice
in women severe acne

high blood cholesterol

and atherosclerosis;
breast enlargement high blood pressure
in men and breast and damage to heart
reduction in women

liver dysfunction
and cancer
kidney disease and
retention of fluids,
called "steroid bloat" in women, increased size
of ovaries; cessation of
ovulation and menstruation

reduced testicular size, low

sperm count, and impotency stunted growth in youngsters
by prematurely halting
activity of the epiphyseal
plates

Figure 10B The effects of anabolic steroid use.

Chapter 10 The Endocrine System 199

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Physiology, Fifth Edition

Figure 10.13 Melatonin production. Melatonin production is Leptin

greatest at night when we are sleeping. Light suppresses
Leptin is a protein hormone produced by adipose tissue. Lep-
melatonin production (a), so its duration is longer in the winter (b)
tin acts on the hypothalamus, where it signals satiety—that
than in the summer (c).
the individual has had enough to eat. Strange to say, the
blood of obese individuals may be rich in leptin. It is possible
that the leptin they produce is ineffective because of a genetic
mutation, or else their hypothalamic cells lack a suitable
number of receptors for leptin.
a.
winter
Growth Factors
A number of different types of organs and cells produce pep-
tide growth factors, which stimulate cell division and mito-
b.
summer
sis. Some, such as lymphokines, are released into the blood;
others diffuse to nearby cells. Growth factors of particular in-
terest are the following:
Granulocyte and macrophage colony-stimulating factor (GM-
c.
CSF) is secreted by many different tissues. GM-CSF
6 P.M. 6 A.M.
causes bone marrow stem cells to form either
granulocyte or macrophage cells, depending on
Thymus Gland whether the concentration is low or high.
Platelet-derived growth factor is released from platelets and
The lobular thymus gland, which lies just beneath the ster- from many other cell types. It helps in wound healing
num (see Fig. 10.1), reaches its largest size and is most active and causes an increase in the number of fibroblasts,
during childhood. Lymphocytes that originate in the bone smooth muscle cells, and certain cells of the nervous
marrow and then pass through the thymus are transformed system.
into T lymphocytes. The lobules of the thymus are lined by Epidermal growth factor and nerve growth factor stimulate the
epithelial cells that secrete hormones called thymosins. These cells indicated by their names, as well as many others.
hormones aid in the differentiation of lymphocytes packed These growth factors are also important in wound
inside the lobules. Although the hormones secreted by the healing.
thymus ordinarily work in the thymus, researchers hope that Tumor angiogenesis factor stimulates the formation of
these hormones could be injected into AIDS or cancer pa- capillary networks and is released by tumor cells. One
tients where they would enhance T-lymphocyte function. treatment for cancer is to prevent the activity of this
growth factor.
Pineal Gland
The pineal gland, which is located in the brain (see Fig. 10.1), Prostaglandins
produces the hormone melatonin, primarily at night. Mela-
Prostaglandins are potent chemical signals produced
tonin is involved in our daily sleep-wake cycle; normally we
within cells from arachidonate, a fatty acid. Prostaglandins
grow sleepy at night when melatonin levels increase and
are not distributed in the blood; instead, they act locally,
awaken once daylight returns and melatonin levels are low
quite close to where they were produced. In the uterus,
(Fig. 10.13). Daily 24-hour cycles such as this are called circa-
prostaglandins cause muscles to contract and may be in-
dian rhythms, and circadian rhythms are controlled by an in-
volved in the pain and discomfort of menstruation. Also,
ternal timing mechanism called a biological clock.
prostaglandins mediate the effects of pyrogens, chemicals
Based on animal research, it appears that melatonin also
that are believed to reset the temperature regulatory center
regulates sexual development. It has also been noted that chil-
in the brain. For example, aspirin reduces body temperature
dren whose pineal gland has been destroyed due to a brain
and controls pain because of its effect on prostaglandins.
tumor experience early puberty.
Certain prostaglandins reduce gastric secretion and have
been used to treat ulcers; others lower blood pressure and
Hormones from Other Tissues have been used to treat hypertension; and still others inhibit
We have already mentioned that the heart produces atrial natri- platelet aggregation and have been used to prevent throm-
uretic hormone (see page 194). And you will see in Chapter 15 bosis. However, different prostaglandins have contrary ef-
that the stomach and small intestine produce peptide hor- fects, and it has been very difficult to successfully standardize
mones that regulate digestive secretions. their use.

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Physiology, Fifth Edition

10.7 Chemical Signals The Importance of Chemical Signals

Chemical signals are molecules that affect the behavior of Cells, organs, and even individuals communicate with one
those cells that have receptor proteins to receive them. For ex- another by using chemical signals.
ample, a hormone that binds to a receptor protein affects the We are most familiar with chemical signals, such as hor-
metabolism of the cell. mones, that are produced by organs some distance from one
Hormones fall into two basic chemical classes. As noted another in the body. Hormones produced by the anterior pi-
in Table 10.1, most are peptide hormones, a category that tuitary, for example, influence the function of numerous or-
includes not only those that are peptides but also proteins, gans throughout the body. Insulin, produced by the pancreas,
glycoproteins, or modified amino acids. The remainder are is transported in blood to the liver and also to all the cells. The
steroid hormones, each having the same four-carbon ring nervous system at times utilizes chemical signals that are pro-
complex, but with different side chains. duced by an organ distant from the one being affected. For ex-
ample, the hypothalamus produces releasing hormones that
travel in a portal system to the anterior pituitary gland.
How Hormones Function Many chemical signals act locally—that is, from cell to
Most peptide hormones bind to a receptor protein in the cell. Prostaglandins are local hormones, and certainly neuro-
plasma membrane. This often leads to the conversion of ATP transmitter substances released by one neuron affect a neuron
to cyclic AMP (cyclic adenosine monophosphate, abbrevi- nearby. Growth factors, which fall into this category, are very
ated cAMP) (Fig. 10.14). In cAMP, one phosphate group is important regulators of cell division. Some growth factors are
attached to the rest of the molecule at two spots. The peptide being used as medicines to promote the production of blood
hormone is called the first messenger, and cAMP is called the cells in AIDS and cancer patients. When a tumor develops, cell
second messenger. (Calcium is also a common second mes- division occurs even when no stimulatory growth factor has
senger, and this helps explain why calcium regulation in the been received. And the tumor produces a growth factor called
body is so important.) The second messenger sets in motion tumor angiogenesis factor, which promotes the formation of
an enzyme cascade, so called because each enzyme in turn capillary networks to service its cells.
activates several others next in line. The binding of a single
peptide hormone can result in as much as a thousandfold Chemical Signals Between Individuals
response. The response can be an end product that leaves
the cell. Chemical signals that act between individuals are called
Steroid hormones are lipids, and therefore they cross the pheromones. Pheromones are well exemplified in other ani-
plasma membrane and other cellular membranes (Fig. mals, but they may also be effective between people. Humans
10.15). Only after they are inside the cell do steroid hor- produce airborne chemicals from a variety of areas, including
mones, such as estrogen and progesterone, bind to receptor the scalp, oral cavity, armpits, genital areas, and feet. For exam-
proteins. The hormone-receptor complex then binds to DNA, ple, the armpit secretions of one woman could possibly affect
activating particular genes. Activation leads to production of a the menstrual cycle of another woman. Women who live in the
cellular enzyme in multiple quantities. same household often have menstrual cycles in synchrony. Also,
the cycle length becomes more normal when women with ir-
regular cycles are exposed to extracts of male armpit secretions.

Figure 10.14 The binding of a peptide hormone leads to Figure 10.15 A steroid hormone results in a hormone-
cAMP and then to activation of an enzyme cascade. receptor complex that activates DNA and protein synthesis.

blood capillary blood capillary

plasma membrane
peptide hormone steroid
(first messenger) hormone protein
synthesis
plasma membrane
nuclear ribosome
envelope
ATP second
cAMP messenger

mRNA
receptor enzyme cascade
hormone-
receptor
complex
end product
(leaves the cell) cytoplasm
cytoplasm DNA

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Physiology, Fifth Edition

10.8 Effects of Aging kidneys to reabsorb sodium, and when the level of sodium
rises, water is automatically reabsorbed so that blood volume
Thyroid disorders and diabetes are the most significant en- and pressure rise. Regulation by the endocrine system often
docrine problems affecting health and function as we age. involves antagonistic hormones; in this case, ANH produced
Both hypothyroidism and hyperthyroidism are seen in the el- by the heart causes sodium excretion.
derly. Graves disease is an autoimmune disease that targets the The endocrine system helps regulate calcium balance. The
thyroid, resulting in symptoms of cardiovascular disease, in- concentration of calcium (Ca2!) in the blood is critical be-
creased body temperature, and fatigue. In addition, a patient cause this ion is important to nervous conduction, muscle
may experience weight loss of as much as 20 pounds, depres- contraction, and the action of hormones. As you know, the
sion, and mental confusion. Hypothyroidism (myxedema) bones serve as a reservoir for calcium. When the blood cal-
may fail to be diagnosed because the symptoms of hair loss, cium concentration lowers, parathyroid hormone promotes
skin changes, and mental deterioration are attributed simply the breakdown of bone and the reabsorption of calcium by
to the process of aging. the kidneys, and the absorption of calcium by the intestines.
The true incidence of IDDM diabetes among the elderly is Opposing the action of parathyroid hormone, calcitonin se-
unknown. Its symptoms can be confused with those of other creted by the thyroid brings about the deposit of calcium in
medical conditions that are present. As in all adults, NIDDM the bones.
diabetes is associated with being overweight and often can be The endocrine system helps regulate response to the external
controlled by proper diet. environment.In “fight-or-flight” situations, the nervous system
The effect of age on the sex organs is discussed in Chap- stimulates the adrenal medulla to release epinephrine (adren-
ter 17. aline), which has a powerful effect on various organs. This,
too, is important to homeostasis because it allows us to be-
have in a way that keeps us alive. Any damage due to stress is
10.9 Homeostasis then repaired by the action of other hormones, including
cortisol. As discussed in the Medical Focus on this page,
The endocrine system and the nervous system work together
glucocorticoid (e.g., cortisone) therapy is useful for its anti-
to regulate the organs of the body and thereby maintain
inflammatory and immunosuppressive effects.
homeostasis. It is clear from reviewing the Human Systems
Work Together illustration on page 203 that the endocrine
system particularly influences the digestive, cardiovascular,
and urinary systems in a way that maintains homeostasis.
The endocrine system helps regulate digestion. The digestive
system adds nutrients to the blood, and hormones produced
by the digestive system influence the gallbladder and pancreas
to send their secretions to the digestive tract. Another hor-
mone, gastrin, promotes the digestion of protein by the stom-
ach. Through its influence on the digestive process, the en-
Glucocorticoid Therapy
docrine system promotes the presence of nutrients in the Glucocorticoids suppress the body’s normal reaction to dis-
blood. ease: the inflammatory reaction (see Fig. 13.4) and the im-
The endocrine system helps regulate fuel metabolism. We often mune process. Thus, glucocorticoid therapy is useful for treat-
associate the level of glucose in the blood with insulin and ing autoimmune diseases such as rheumatoid arthritis, organ
glucagon. Just after eating, insulin encourages the uptake of transplant rejection, allergies, and severe asthma. However,
glucose by cells and the storage of glucose as glycogen in the long-term administration of glucocorticoids for therapeutic
liver and muscles. In between eating, glucagon stimulates the purposes causes some degree of Cushing syndrome (see page
liver to break down glycogen to glucose so that the blood level 195). In addition, sudden withdrawal from glucocorticoid
stays constant. Adrenaline from the adrenal medulla also stim- therapy causes symptoms of diminished secretory activity by
ulates the liver to release glucose. Glucagon (from the pancreas) the adrenal cortex. This occurs because glucocorticoids sup-
and cortisol (from the adrenal cortex) promote the breakdown press the release of adrenocorticotropic hormone (ACTH) by
of protein to amino acids, which can be converted to glucose the anterior pituitary and lead to a decrease in glucocorticoid
by the liver. They also promote the metabolism of fatty acids to production by the adrenal cortex. Therefore, withdrawal of
conserve glucose, a process called glucose sparing. glucocorticoids following long-term use must be tapered. Dur-
The endocrine system helps regulate blood pressure and vol- ing an alternate-day schedule, the dosage is gradually reduced
ume.ADH produced by the hypothalamus but secreted by the and then finally discontinued as the patient’s adrenal cortex
posterior pituitary promotes reabsorption of water by the kid- resumes activity.
neys, especially when we have not been drinking water that
day. Aldosterone produced by the adrenal cortex causes the

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Physiology, Fifth Edition

Human Systems Work Together ENDOCRINE SYSTEM

Growth hormone and

androgens promote growth
of skeletal muscle;
epinephrine stimulates
heart and constricts blood
vessels.

Cardiovascular System

Chapter 10 The Endocrine System 203

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Human Anatomy & Coordination Companies, 2004
Physiology, Fifth Edition

Selected New Terms

Basic Key Terms peptide hormone (pep’tid hor’mon), p. 201
adrenal cortex (uh-dre’nul kor’teks), p. 193 pineal gland (pin’e-ul gland), p. 200
adrenal gland (uh-dre’nul gland), p. 193 pituitary gland (pI-tu’I-tar”e gland), p. 188
adrenal medulla (uh-dre’nul mE-dul’uh), p. 193 posterior pituitary (pos-ter’e-or pI-tu’I-tar”e), p. 188
adrenocorticotropic hormone (uh-dre’no-kor”ti-ko-trop’ik positive feedback (poz’I-tiv fed’bak), p. 188
hor’mon), p. 188 progesterone (pro-jes’ter-on), p. 198
aldosterone (al”dos’ter-on), p. 194 prolactin (pro-lak’tin), p. 188
anabolic steroid (an”uh-bol’ik stE’royd), p. 198 prostaglandins (pros”tuh-glan’dinz), p. 200
androgen (an’dro-jen), p. 198 renin (re’nin), p. 194
anterior pituitary (an-ter’e-or pI-tu’I-tar”e), p. 188 steroid hormone (ster’oyd hor’mon), p. 201
antidiuretic hormone (an”tI-di”yu-ret’ik hor’mon), p. 188 testis (tes’tis), p. 198
atrial natriuretic hormone (a’tre-al na”tre-yu-ret’ik hor’mon), testosterone (tes-tos’tE-ron), p. 198
p. 194 thymosin (thi’mo-sin), p. 200
calcitonin (kal”sI-to’nin), p. 192 thymus gland (thi’mus gland), p. 200
circadian rhythm (ser”ka’de-an rI’thm), p. 200 thyroid gland (thi’royd gland), p. 191
cortisol (kor’tI-sol), p. 194 thyroid-stimulating hormone (thi’royd stim’yu-lat-ing
cyclic AMP (sik’lik AMP), p. 201 hor’mon), p. 188
endocrine gland (en’do-krin gland), p. 186 thyroxine (thi-rok’sin), p. 191
epinephrine (ep”I-nef’rin), p. 193
estrogen (es’tro-jen), p. 198
Clinical Key Terms
glucagon (glu’kuh-gon), p. 196 acidosis (as”I-do’sis), p. 198
glucocorticoid (glu”ko-kor’tI-koyd), p. 193 acromegaly (ak”ro-meg’uh-le), p. 190
gonad (go’nad), p. 198 Addison disease (A’dI-son dI-zez’), p. 195
gonadotropic hormone (go”nad-o-trop’ik hor’mon), p. 188 cretinism (kre’tI-nizm), p. 191
growth factor (groth fak’tor), p. 200 Cushing syndrome (koosh’ing sin’drom), p. 195
growth hormone (groth hor’mon), p. 188 diabetes insipidus (di”uh-be’tez in-sip’I-dus), p. 188
hormone (hor’mon), p. 186 exophthalmic goiter (ek”sof-thal’mik goy’ter), p. 191
hypothalamic-inhibiting hormone (hi”po-thE-lam’ik- glycosuria (gli’ko-sur’e-uh), p. 198
in-hib’it-ing hor’mon), p. 188 Graves disease (gravz dI-zez’), p. 191
hypothalamic-releasing hormone (hi”po-thE-lam’ik-re-les’- hyperglycemia (hi”per-gli-se’me-uh), p. 198
ing hor’mon), p. 188 hypoglycemia (hi”po-gli-se’me-uh), p. 198
hypothalamus (hi”po-thal’uh-mus), p. 188 insulin-dependent diabetes mellitus (in’sul-in-de-pen’dent
insulin (in’suh-lin), p. 196 di”uh-be’tez mE-li’tus), p. 198
leptin (lep’tin), p. 200 ketonuria (ke”to-nu’re-uh), p. 198
melatonin (mel”uh-to’nin), p. 200 myxedema (mik”sE-de’muh), p. 191
mineralocorticoids (min”er-al-o-kor’tI-koyds), p. 193 noninsulin-dependent diabetes (non’in’sul-in-de-pen’dent
norepinephrine (nor”ep-I-nef’rin), p. 193 di”uh-be’tez), p. 198
ovary (o’var-e), p. 198 pituitary dwarfism (pI-tu’I-tar”e dwarf’-izm), p. 190
oxytocin (ok”sI-to’sin), p. 188 polydipsia (pol”e-dip’se-uh), p. 198
pancreas (pan’kre-us), p. 196 polyphagia (pol”e-fa-je-uh), p. 198
pancreatic islets (of Langerhans) (pan”kre-at’ik i’lets ov polyuria (pol”e-yu-re-uh), p. 198
lahng’er-hanz), p. 196 simple goiter (sim’pl goy’ter), p. 191
parathyroid gland (par”uh-thi’royd gland), p. 192 tetany (tet’uh-ne), p. 192
parathyroid hormone (par”uh-thi’royd hor’mon), p. 192

204 Part III Integration and Coordination

 Mader: Understanding III. Integration and 10. The Endocrine System © The McGraw−Hill
Human Anatomy & Coordination Companies, 2004
Physiology, Fifth Edition

Summary
10.1 Endocrine Glands 10.4 Adrenal Glands B. Tissues also produce hormones.
Endocrine glands secrete hormones The adrenal glands respond to stress: Adipose tissue produces leptin,
into the bloodstream, and from there Immediately, the adrenal medulla which acts on the hypothalamus,
they are distributed to target organs or secretes epinephrine and and various tissues produce growth
tissues. The major endocrine glands norepinephrine, which bring about factors. Prostaglandins are
and hormones are listed in Table 10.1. responses we associate with emergency produced and act locally.
Negative feedback controls the situations. On a long-term basis, the 10.7 Chemical Signals
secretion of hormones, and adrenal cortex produces the A. Hormones are either peptides or
antagonistic hormonal actions control glucocorticoids (e.g., cortisol) and the steroids. Reception of a peptide
the effect of hormones. mineralocorticoids (e.g., aldosterone). hormone at the plasma membrane
10.2 Hypothalamus and Pituitary Gland Cortisol stimulates hydrolysis of activates an enzyme cascade inside
A. Neurosecretory cells in the proteins to amino acids that are the cell. Steroid hormones
hypothalamus produce antidiuretic converted to glucose; in this way, it combine with a receptor in the
hormone (ADH) and oxytocin, raises the blood glucose level. cell, and the complex attaches to
which are stored in axon endings in Aldosterone causes the kidneys to and activates DNA. Protein
the posterior pituitary until they are reabsorb sodium ions (Na!) and to synthesis follows.
released. excrete potassium ions (K!). Addison B. In the human body, some chemical
B. The hypothalamus produces disease develops when the adrenal signals, such as traditional
hypothalamic-releasing and cortex is underactive, and Cushing endocrine hormones and secretions
hypothalamic-inhibiting syndrome develops when the adrenal of neurosecretory cells, act at a
hormones, which pass to the cortex is overactive. distance. Others, such as
anterior pituitary by way of a portal 10.5 Pancreas prostaglandins, growth factors, and
system. The anterior pituitary The pancreatic islets secrete insulin, neurotransmitters, act locally.
produces at least six types of which lowers the blood glucose level, Whether humans have pheromones
hormones, and some of these and glucagon, which has the opposite is under study.
stimulate other hormonal glands to effect. The most common illness 10.8 Effects of Aging
secrete hormones. caused by hormonal imbalance is Two concerns often seen in the elderly
10.3 Thyroid and Parathyroid Glands diabetes mellitus, which is due to the are thyroid malfunctioning and
The thyroid gland requires iodine to failure of the pancreas to produce diabetes mellitus.
produce triiodothyronine and insulin and/or the failure of the cells 10.9 Homeostasis
thyroxine, which increase the to take it up. Hormones particularly help maintain
metabolic rate. If iodine is available in 10.6 Other Endocrine Glands homeostasis in several ways:
limited quantities, a simple goiter A. The gonads produce the sex Hormones help maintain the level of
develops; if the thyroid is overactive, hormones. The thymus secretes nutrients (e.g., amino acids and
an exophthalmic goiter develops. The thymosins, which stimulate T- glucose in blood); help maintain
thyroid gland also produces calcitonin, lymphocyte production and blood volume and pressure by
which helps lower the blood calcium maturation. The pineal gland regulating the sodium content of the
level. The parathyroid glands secrete produces melatonin, which may be blood; help maintain the blood
parathyroid hormone, which raises the involved in circadian rhythms and calcium level; help regulate fuel
blood calcium and decreases the the development of the metabolism; and help regulate our
blood phosphate levels. reproductive organs. response to the external environment.

Study Questions
1. Describe a mechanism by which the hypothalamus, the anterior pituitary, 6. How do the thyroid and the
secretion of a hormone is regulated and and other endocrine glands. (p. 188) parathyroid work together to control
another by which the effect of a 4. Discuss the effect of growth hormone the blood calcium level? (p. 192)
hormone is controlled. (p. 186) on the body and the result of having 7. How do the adrenal glands respond to
2. Explain the relationship of the too much or too little growth hormone stress? What hormones are secreted by
hypothalamus to the posterior pituitary when a young person is growing. What the adrenal medulla, and what effects
gland and to the anterior pituitary is the result if the anterior pituitary do these hormones have? (p. 193)
gland. List the hormones secreted by produces growth hormone in an adult? 8. Name the most significant
the posterior and anterior pituitary (p. 190) glucocorticoid and mineralocorticoid,
glands. (pp. 187–88) 5. What types of goiters are associated and discuss their functions. Explain the
3. Give an example of the negative with a malfunctioning thyroid? Explain symptoms of Addison disease and
feedback relationship among the each type. (p. 191) Cushing syndrome. (pp. 194–95)

Chapter 10 The Endocrine System 205

 Mader: Understanding III. Integration and 10. The Endocrine System © The McGraw−Hill
Human Anatomy & Coordination Companies, 2004
Physiology, Fifth Edition

9. Draw a diagram to explain how insulin the functions of the hormones they 13. Contrast hormonal and neural signals,
and glucagon maintain the blood secrete. (pp. 198, 200) and show that there is an overlap
glucose level. Use your diagram to 11. What are leptin, growth factors, and between the mode of operation of the
explain the major symptoms of type I prostaglandins? How do these nervous system and that of the
diabetes mellitus. (pp. 196, 198) substances act? (p. 200) endocrine system. (p. 201)
10. Name the other endocrine glands 12. Explain how peptide hormones and 14. Discuss five ways the endocrine system
discussed in this chapter, and discuss steroid hormones affect the metabolism helps maintain homeotasis. (p. 202)
of the cell. (p. 201)

Objective Questions
Fill in the blanks. 6. Parathyroid hormone increases the level 11. Whereas hormones
1. Generally, hormone production is self- of in the blood. are lipid soluble and bind to receptor
regulated by a 7. Adrenocorticotropic hormone (ACTH), proteins within the cytoplasm of target
mechanism. produced by the anterior pituitary, cells, hormones
2. The hypothalamus stimulates the of bind to membrane-bound receptors,
the hormones and the adrenal glands. thereby activating second messengers.
, released by the 8. An overproductive adrenal cortex results 12. Whereas the adrenal
posterior pituitary. in the condition called is under the
3. The secreted by . control of the autonomic nervous
the hypothalamus control the anterior 9. Type I diabetes mellitus is due to a system, the adrenal
pituitary. malfunctioning , secretes its hormones in response to
4. Growth hormone is produced by the but type II diabetes is due to from the anterior
pituitary. malfunctioning . pituitary gland.
5. Simple goiter occurs when the thyroid 10. Prostaglandins are not carried in the
is producing (too as are hormones
much or too little) . secreted by the endocrine glands.

Medical Terminology Reinforcement Exercise

Consult Appendix B for help in 5.lactogenic (lak”to-jen’ik) 11. ketoacidosis (ke’to-as’I-do’sis)
pronouncing and analyzing the meaning 6.adrenopathy (ad”ren-op’uh-the) 12. thyroiditis (thi-roy-di’tis)
of the terms that follow. 7.adenomalacia (ad”E-no-muh-la’she-uh) 13. glucosuria (glu-co-su’re-uh)
8.parathyroidectomy (par”uh-thi”roy- 14. microsomia (mi’kro-so’me-uh)
1. antidiuretic (an”tI-di”yu-ret’ik)
dek’to-me) 15. androgenic alopecia (an’dro-jen’ik al-o-
2. hypophysectomy (hi-pof”I-sek’to-me)
9. polydipsia (pol”e-dip’se-uh) pe’she-uh)
3. gonadotropic (go”nad-o-trop’ik)
10. dyspituitarism (dis-pI-tu’I-ter’izm)
4. hypokalemia (hi”po-kal”e’me-uh)

Website Link
Visit the Student Edition of the Online Learning Center at http://www.mhhe.com/maderap5 for additional quizzes, interactive learning
exercises, and other study tools.

206 Part III Integration and Coordination