Endocrine Glands and Their Hormones ▪ Also known as pars intermedia

Chapter 13 – Human Anatomy and Physiology ▪ It is the boundary between the anterior
and posterior lobes of the pituitary
▪ The endocrine system consists of ductless
gland
glands that secrete hormones into the
▪ In human fetal life, this area produces
interstitial fluid and then the blood
melanocyte-stimulating hormone
▪ The organs in the body with the richest
(MSH) which causes the release of
blood supply are the endocrine glands, such
melanin pigment in skin melanocytes
as the adrenal gland and the thyroid gland
▪ The pars intermedia is normally either
▪ Some glands of the endocrine system
very small or entirely absent in
perform functions in addition to hormone
adulthood
secretion
▪ For example, the endocrine portion of the Posterior Pituitary Gland
pancreas has cells that secrete hormones,
▪ Also known as neurohypophysis or pars
whereas the much larger exocrine portion
posterior
of the pancreas secretes digestive enzymes
▪ It is an extension of the brain and is
▪ Portions of the ovaries and testes produce
composed mainly of glial-like cells called
oocytes (female sex cells) and sperm cells
pituicytes
(male sex cells), respectively
▪ Pituicytes do not secrete hormones but
Pituitary Gland and Hypothalamus they act simply as supporting structure for
Section 13-1 large numbers of terminal nerve fibers and
terminal nerve endings from fiber tracts
▪ The pituitary gland is also called the
that originate in the supraoptic and
hypophysis
paraventricular nuclei of the hypothalamus
▪ It is a small gland (1 cm in diameter and 0.5
▪ These tracts pass to the neurohypophysis
to 1 g in weight) about the size of a pea,
through the infundibulum or pituitary stalk
which rests in a depression of the sphenoid
bone (sella turcica) inferior to the Hormones from the pituitary gland control the
hypothalamus of the brain functions of many other glands in the body,
▪ The hypothalamus is an important such as the ovaries, testes, the thyroid gland,
autonomic nervous system and endocrine and the adrenal cortex
control center of the brain located inferior
The pituitary gland also secretes hormones that
to the thalamus
influence growth, kidney function, birth, and
▪ The pituitary glands lies posterior to the
milk production by the mammary glands
optic chiasm and is connected to the
hypothalamus by a stalk called the Historically, the pituitary gland is also known as
infundibulum the master gland because it controls the
▪ The pituitary gland is divided into three function of so many other glands
parts – the anterior pituitary gland, the
However, we now know that the hypothalamus
intermediate lobe, and the posterior
controls the pituitary gland in two ways:
pituitary gland
hormonal control and direct innervation
Anterior Pituitary Gland
HORMONAL CONTROL OF ADENOHYPOPHYSIS
▪ Also known as adenohypophysis or pars
▪ Neurons of the hypothalamus produce and
anterior
secrete neuropeptides that act on cells of the
▪ It is made up of epithelial cells from
anterior pituitary gland
Rathke’s pouch, which is an embryonic
▪ They act as either releasing hormones or
invagination of the pharyngeal
inhibiting hormones
epithelium
▪ Each releasing hormone stimulates the
▪ There are five cell types of the anterior
production and secretion of a specific hormone
pituitary gland: somatotropes (30% to
by the anterior pituitary
40%), corticotropes (20%), thyrotropes
▪ Each inhibiting hormone decreases the
(3% to 5%), gonadotropes (3% to 5%),
secretion of a specific anterior pituitary
and lactotropes (3% to 5%)
hormone
Intermediate Lobe
 ▪ Releasing and inhibiting hormones enter a
capillary bed in the hypothalamus and are
transported through veins to a second capillary
bed in the anterior pituitary
▪ There they leave the blood and bind to
membrane-bound receptors involved with
regulating anterior pituitary hormone secretion
▪ The capillary beds and veins that transport the
releasing and inhibiting hormones are called the
hypothalamic-pituitary portal system or
hypophyseal-hypothalamic tract
DIRECT INNERVATION OF THE NEUROHYPOPHYSIS
▪ Stimulation of neurons within the
hypothalamus controls the secretion of
hormones from the posterior pituitary
▪ The cell bodies of these neurons are in the
hypothalamus, and their axons extend through
the infundibulum to the posterior pituitary
▪ Hormones are produced in the nerve cell bodies
and are transported through the axons to the
posterior pituitary, where they are stored in the
axon endings
▪ When these nerve cells are stimulated, action
potentials from the hypothalamus travel along
the axons to the posterior pituitary and cause
the release of hormones from the axon endings
▪ Within the hypothalamus and pituitary gland,
the nervous and endocrine systems are closely
interrelated
▪ Emotions such as joy and anger, as well as
chronic stress, influence the endocrine system
through the hypothalamus
▪ Conversely, hormones of the endocrine system
can influence the functions of the
hypothalamus and other parts of the brain
HORMONES OF THE ADENOHYPOPHYSIS
Growth Hormone (GH)
▪ Growth hormone is a small protein molecule
that contains 191 amino acids in a single chain
and has a molecular weight of 22,005
▪ Stimulates the growth of bones, muscles, and
other organs by increasing gene expression
▪ Promotes increased cell size and increased
mitosis with development of increased numbers
of cells and specific differentiation of certain
types of cells such as bone growth cells and
early muscle cells
▪ GH has many specific metabolic effects as well:
1. Increased rate of protein synthesis in all
cells of the body
2. Increased mobilization of fatty acids
from adipose tissue, increased free
fatty acids (FFA) in the blood, and
increased use of fatty acids for energy
3. Decreased rate of glucose utilization
throughout the body
▪ Thus, in effect, GH enhances the body protein,
uses up the fat stores, and conserves
carbohydrates
▪ Necessity of insulin and carbohydrate for the
growth-promoting action of GH
o GH fails to cause growth in an animal
that lacks a pancreas and also fails to
cause growth if carbohydrates are
excluded from diet
o Therefore, adequate insulin activity as
well as availability of carbohydrates are
necessary for GH to be effective
o Part of this requirement is to provide
the energy needed for the metabolism
of growth
o Insulin also enhances the transport of
amino acids into cells in the same way
that it enhances glucose transport
 Stimulation of Cartilage and Bone Growth
o Increased deposition of protein by the
chondrocytic and osteogenic cells that
cause bone growth
o Increased rate of reproduction of these
cells as well
o Specific effect of converting
chondrocytes into osteogenic cells, thus
causing specific deposition of new bone
▪ GH exerts much of its effects through
intermediate substances called somatomedins
or insulin-like growth factors (IGF)
▪ GH increases IGF secretion from tissues
such as the liver, and the IGF molecules
bind to receptors on the cells of tissues
such as bone and cartilage, where they
stimulate growth
▪ The IGF are similar in structure to
insulin and can bind, to some degree, to
insulin receptors
▪ Also, insulin, at high concentrations, can
bind to IGF receptors
▪ Regulation of Growth Hormone Secretion
 ▪ It was believed that GH was secreted
primarily during the period of growth
but then disappeared from the blood at
adolescence
▪ This was proven to be untrue because
after adolescence, GH secretion
decreases only slowly with aging, finally
falling to about 25 percent of the
adolescent level in very old age
▪ The rate of growth hormone secretion
increases and decreases within minutes
▪ This is in relation to the person’s state
of nutrition or stress:
1. Starvation, especially with severe
protein deficiency
2. Hypoglycemia or low concentration of
fatty acids in the blood
3. Exercise
4. Excitement
5. Trauma
▪ GH increases during the first two hours of deep
sleep
▪ Most people have a rhythm of GH secretion,
with daily peak levels occurring during deep
sleep
▪ GH secretion also increases during periods of
fasting and exercise
▪ Blood GH levels do not become greatly elevated
during periods of rapid growth, although
children tend to have somewhat higher blood
levels than do adults
▪ In addition to GH, genetics, nutrition, and sex
hormones influence growth
▪ Normal concentration of GH in the plasma of an
adult is between 1.6 and 3 ng/mL
▪ In a child or adolescent, it is about 6 ng/mL
▪ Values often increase to as high as 50 ng/mL
after depletion of body stores of proteins or
carbohydrates during prolonged starvation
Role of Hypothalamus, GHRH, and GHIH in Control
of GH Secretion
 GH secretion is controlled almost entirely in
response to two factors secreted in the
hypothalamus and then transported to the
adenohypophysis through the
hypothalamic-hypophyseal portal vesselS
 They are growth hormone releasing
hormone (GHRH) and growth hormone
inhibiting hormone (GHIH) or somatostatin
 Both are polypeptides with GHRH
containing 144 amino acids and GHIH
containing 14 amino acids
 Ventromedial nucleus of the hypothalamus
is responsible for GHRH secretion, which is
the same area of the hypothalamus that is
known to be sensitive to hypoglycemia and
to cause hunger in hypoglycemic states
 Secretion of somatostatin is controlled by
other nearby areas of the hypothalamus
 Hypothalamic signals depicting emotions,
stress, and trauma can all affect
hypothalamic control of GH secretion
 Catecholamines, dopamine, and serotonin,
each of which is released by a different
neuronal system in the hypothalamus,
increase the rate of GH secretion
 Most of control of GH secretion is mediated
through GHRH rather than through the
somatostatin
GHRH stimulates GH secretion by attaching to
membrane-bound receptors on somatotropes
 Aside from inhibiting GH secretion,
somatostatin also inhibits the release of
glucagon and insulin from the α and β cells of
the pancreas respectively
 Somatostatin is also secreted by delta cells of
the islets of Langerhans of the pancreas
Pathophysiology
▪ Too little growth hormone secretion can result
from abnormal development of the pituitary
gland
▪ A young person suffering from growth hormone
deficiency remains small, although normally
proportioned, and is called a pituitary dwarf
▪ This condition can be treated by administering
growth hormone
▪ Excess growth hormone secretion can result
from hormone-secreting tumors of the pituitary
gland
▪ If excess growth hormone is present before
bones finish growing in length, exaggerated
bone growth occurs and the person becomes
abnormally tall, a condition called gigantism
▪ If excess hormone is secreted after growth in
bone length is complete, growth continues in
bone diameter only
▪ As a result, the facial features and hands
become abnormally large, a condition called
acromegaly
Thyroid-Stimulating Hormone (thyrotropin or TSH)
 ▪ TSH binds to membrane-bound receptors on
cells of the thyroid gland and causes the cells to
secrete thyroid hormones
▪ When too much TSH is secreted, the thyroid
gland enlarges and secretes too much thyroid
hormones
▪ When too little TSH is secreted, the thyroid
gland decreases in size and secretes too little
thyroid hormone
▪ The rate of TSH secretion is regulated by a
releasing hormone (thyrotopin-releasing
hormone or TRH) from the hypothalamus
Adrenocorticotropic Hormone (ACTH)
▪ Binds to membrane-bound receptors on
Melanocyte-Stimulating Hormone (MSH)
cells of the adrenal cortex
▪ Increases the secretion of a hormone from
the adrenal cortex called cortisol, also
called hydrocortisone
▪ ACTH is required to keep the adrenal cortex
from degenerating
▪ Also binds to melanocytes in the skin and
increase skin pigmentation; one sign of too
much ACTH secretion is darkening of the
skin
▪ Rate of ACTH secretion is increased by
corticotropin-releasing hormone (CRH) or
factor (CRF), from the hypothalamus
Gonadotropins
▪ These hormones bind to the membrane
receptors on cells of the gonads (ovaries and
testes)
▪ Regulate growth, development, and functions
of the gonads
▪ In females, luteinizing hormone (LH) causes the
ovulation of oocytes and the secretion of
hormones estrogen and progesterone from the
ovaries
▪ In males, LH stimulates interstitial cells of the
testes to secrete sex hormone testosterone and
thus is sometimes referred to as interstitial cell-
stimulating hormone (ICSH)
▪ Follicle-stimulating hormone (FSH) stimulates
the development of follicles in the ovaries and
sperm cells in the testes
▪ Without LH and FSH, the ovaries and testes
decrease in size, no longer produce oocytes or
sperm cells, and no longer secrete hormones
▪ A single releasing hormone from the
hypothalamus called gonadotropin-releasing
hormone (GnRH) increases the secretion of
both LH and FSH
Prolactin (PRL)
▪ Also known as luteotropic hormone or
luteotropin
▪ Binds to membrane-bound receptors in
cells (lactotrophs) of the breast where it
helps promote development of the breast
during pregnancy and stimulates
production of milk during pregnancy
▪ Main regulatory hormone of prolactin is
prolactin inhibitory hormone (PIH) which
inhibits prolactin secretion
▪ TRH has a stimulatory effect on PRL release;
however, PRL is the only adenohypophyseal
hormone whose principal control is
inhibitory
▪ Binds to membrane-bound receptors on
melanocytes and causes them to synthesize
melanin
▪ Structure of MSH is similar to ACTH, and
over secretion of either hormone causes
the skin to darken
▪ Regulation of MSH is not well understood,
but there appears to be two regulatory
hormones from the hypothalamus – one
that increases MSH secretion and one that
decreases it
Antidiuretic Hormone (ADH) or Vasopressin
▪ Primarily synthesized in the supraoptic
nuclei of the hypothalamus
▪ Although the paraventricular nuclei of the
hypothalamus primarily produce oxytocin, it
can also synthesize one-sixth as much of
ADH
▪ ADH is a polypeptide containing nine amino
acids
▪ Binds to membrane-bound receptors on
cells of the DCT and collecting ducts of the
kidneys, thereby increasing water
reabsorption by these structures
▪ In the absence of ADH, the DCT and
collecting ducts of the kidneys are
impermeable to water, which prevents
significant reabsorption of water and
therefore allows extreme loss of water into
the urine, causing extreme dilution of urine
▪ In the presence of ADH, the permeability of
the DCT and collecting ducts to water
increases greatly and allows most of the
water to be reabsorbed as the tubular fluid
passes through these ducts, thereby
conserving water in the body and producing
very concentrated urine
▪ Regulation of ADH production is by means
of osmotic regulation
 ▪ Somewhat in or near the hypothalamus are
modified neuron receptors called
osmoreceptors
▪ When the ECF becomes too concentrated,
fluid is pulled by osmosis out of the
osmoreceptors cell, decreasing its size and
initiating appropriate nerve signals in the
supraoptic nuclei of the hypothalamus to
cause additional ADH secretion
▪ Conversely, when the ECF becomes too
dilute, water moves by osmosis in the
opposite direction into the osmoreceptors,
and this decreases the signal for ADH
secretion
▪ Higher concentrations of ADH also have a
potent effect of constricting the arterioles
everywhere in the body and therefore
increasing the arterial pressure
▪ For this reason, ADH is also known as
vasopressin
▪ One of the stimuli for causing intense ADH
secretion is decreased blood volume
▪ A lack of ADH secretion causes diabetes
insipidus, which is the production of a large
amount of dilute urine
▪ The diuretic actions of alcohol are due to its
inhibition of ADH secretion
Oxytocin
▪ Polypeptide containing nine amino acids
▪ Powerfully stimulates the pregnant uterus
by causing it to contract especially towards
the end of gestation
▪ Many obstetricians believe that this
hormone is at least partially responsible for
effecting birth
▪ Oxytocin also plays an important role in
lactation
▪ In lactation, it causes milk to be expressed
from the alveoli into the ducts so that the
baby can obtain it by suckling
▪ Suckling stimuli on the nipple of the breast
cause signals to be transmitted through the
sensory nerves to the brain
▪ Signals reach the paraventricular and
supraoptic nuclei of the hypothalamus,
causing release of oxytocin by the
neurohypophysis
▪ Oxytocin is then carried by blood to the
breasts, where it causes contraction of
myoepithelial cells that lie outside of and
form a latticework surrounding the alveoli
of the mammary glands
▪ In less than a minute after the beginning of
suckling, milk begins to flow – a process
called milk letdown or milk ejection
THYROID GLAND SECTION 13-2
▪ The thyroid gland is made up of two lobes
connected by a narrow band called the
isthmus
▪ It is located immediately below the larynx
on either side of and anterior to the trachea
▪ It is one of the largest endocrine glands
▪ It appears redder than the surrounding
tissues because it is highly vascular
▪ It is surrounded by a connective tissue
capsule
▪ The thyroid gland secretes two significant
hormones, thyroxine (T4) and triiodothyronine
(T3), that have the profound effect of increasing
the metabolic rate of the body (basal metabolic
rate or BMR)
▪ It also secretes calcitonin, a hormone for
calcium metabolism
▪ Complete lack of thyroid secretion causes the
BMR to fall 40% to 50% below normal, and
extreme excesses of thyroid secretion can cause
the BMR to rise 60% to 100% above normal
▪ Thyroid secretion is controlled primarily by
thyroid-stimulating hormone (TSH), secreted by
the thyrotropes of the anterior pituitary
THYROID HORMONE
▪ About 93 percent of metabolically active
thyroid hormones secreted by the thyroid
gland is thyroxine and 7 percent is
triiodothyronine
▪ However, almost all the thyroxine is
eventually converted to triiodothyronine in
the tissues, so that both are important
functionally
▪ The functions of the two hormones are
qualitatively the same, but they differ in
rapidity and intensity of action
▪ T3 is about 4 times as potent as T4, but it is
present in the blood in much smaller
quantities and persists for a much shorter
time than does T4
▪ Thyroid gland is composed of large numbers
of closed follicles filled with a secretory
substance called colloid and lined with
cuboidal epithelial cells that secrete into
the interior of the follicles
 ▪ Major constituent of colloid is the large
glycoprotein thyroglobulin, which contains
the thyroid hormones within its molecule
▪ Once the secretion has entered the follicles,
it must be absorbed back through the
follicular epithelium into the blood before it
can function in the body
▪ The thyroid gland has a blood flow about
five times the weight of the gland each
minute
THYROID HORMONE SYNTHESIS AND SECRETION
Iodine Requirements for Formation of Thyroxine
▪ To form normal quantities of T4, about 50
mg of ingested iodine in the form of iodides
are required each year, or about 1 mg/week
▪ To prevent iodine deficiency, common table
salt is iodized with about 1 part sodium
iodide to every 100,000 parts sodium
chloride
▪ Iodides ingested orally are absorbed from
the gastrointestinal tract
▪ Normally, only 1/5 of iodides in the blood
are removed by the thyroid gland for
synthesis of thyroid hormones, and the rest
are rapidly excreted by kidneys
1. Iodide trapping
2. Formation and secretion of thyroglobulin
3. Oxidation of the iodide ion
4. Organification of thyroglobulin
5. Storage of thyroglobulin
6. Release of thyroxine and triiodothyronine from
the thyroid gland
Iodide Trapping
▪ First stage in the formation of thyroid hormones
is transport of iodides from the blood into the
thyroid glandular cells and follicles
▪ Basal membrane of the thyroid cell has the
specific ability to pump iodide actively to the
interior of the cell – iodide trapping
▪ In a normal thyroid gland, the iodide pumping
concentrates the iodide to about 30 times its
concentration in the blood
▪ When the thyroid gland becomes maximally
active, the concentration ratio can rise to as
high as 250 times
▪ Iodide pumping consists of the following
carrier-mediated transport mechanisms:
o Sodium-potassium pump at the basal
membrane
o Sodium/iodide symporter (NIS) at the
basal membrane
o Pendrin (sodium-independent
chloride/iodide transporter) at the
apical membrane
Formation and Secretion of Thyroglobulin
▪ Thyroid cells are typical protein-secreting
glandular cells
▪ ER and Golgi apparatus synthesize and
secrete into the follicles a large glycoprotein
called thyroglobulin
▪ Each thyroglobulin contains 70 tyrosine
residues, which are the major substrates
that combine with iodine to form thyroid
hormones that form within the
thyroglobulin molecule
▪ T4 and T3 hormones formed from tyrosine
remain a part of thyroglobulin during
synthesis and are stored in the follicular
colloid
▪ In addition to secreting thyroglobulin, the
glandular cells process the iodine and
provide the enzymes and other substances
necessary for thyroid hormone synthesis
Oxidation of the Iodide Ion
▪ Next essential step in thyroid hormone
synthesis is oxidation of iodide ions to either
nascent iodine (I0) or I3-, which is then capable
of combining directly with the amino acid
tyrosine of thyroglobulin
▪ The oxidation process is catalyzed by the
enzyme peroxidase and requires the presence
of another reactant, hydrogen peroxide
Organification of Thyroglobulin
▪ Binding of oxidized iodine with tyrosine
residues of thyroglobulin is called
organification of thyroglobulin
▪ In thyroid cells, oxidized iodine is associated
with an iodinase enzyme that causes the
process to occur in seconds or minutes
 ▪ Oxidized iodine binds with 1/6 of
thyroglobulin tyrosine residues
▪ Major product of the coupling reaction is
thyroxine, which remains part of the
thyroglobulin molecule
▪ Triiodothyronine represents about 1/15 of
the stored hormone
Storage of Thyroglobulin
▪ After synthesis of thyroid hormones, each
thyroglobulin molecule contains 1 to 3
thyroxine molecules and an average of 1
triiodothyronine for every 14 molecules of
thyroxine
▪ In this form, the thyroid hormones are
stored in the follicles in an amount
sufficient to supply the body with its normal
requirements of thyroid hormones for 2 to
3 months
Release of Thyroxine and Triiodothyronine from the
Thyroid Gland
▪ This process occurs as follows:
1. Apical surface of thyroid cells sends
out pseudopod extensions that
close around small portions of the
colloid to form pinocytic vesicles
that enter the apex of the thyroid
cell
2. Lysosomes fuse with these vesicles
containing the colloid
3. The enzyme proteases (hydrolytic
enzyme) from these lysosomes
digest the thyroglobulin, releasing
T4 and T3
4. The free T4 and T3 diffuse through
the basal membrane of the thyroid
cell into the surrounding capillaries
▪ Therefore, thyroglobulin is not released into
the circulating blood
▪ About 3/4 of iodinated tyrosine in
thyroglobulin never becomes thyroid
hormones but remains as
monoiodotyrosine (MIT) and diiodotyrosine
(DIT)
▪ During digestion by proteases, MIT and DIT
are also freed from thyroglobulin; however,
they are not secreted into the blood
▪ Enzyme deiodinase cleaves iodine from
freed MIT and DIT, making the cleaved
iodine molecules available for forming
additional thyroid hormones
DAILY RATE OF T4 AND T3 SECRETION
▪ About 93 percent of thyroid hormone
secreted is normally thyroxine and only 7
percent is triiodothyronine
▪ However, during the ensuing few days,
most of thyroxine is slowly deiodinated to
form triiodothyronine
▪ Therefore, the hormone finally delivered to
and used by tissues is mainly
triiodothyronine, a total of 35 micrograms
of T3 each day
▪ Another 35 micrograms of so-called reverse
T3 is formed each day due to removal of
iodine (“wrong iodine”) from the carboxyl
end instead of the hydroxyl end of
thyroxine
▪ Reverse T3 is almost totally inactive and
eventually destroyed
T4 AND T3 TRANSPORT TO TISSUES
▪ In the blood, all but a fraction of 1 percent
of T4 and T3 combine immediately with
plasma proteins, mainly thyroxine-binding
globulin (TBG), but less so with thyroxine-
binding prealbumin and albumin
▪ Because of high affinity of plasma proteins,
thyroid hormones are released to tissue
cells slowly
▪ Half of T4 in blood is released to tissue cells
every 6 days, whereas half of T3 is released
to the cells in about 1 day
▪ On entering tissue cells, both of these
thyroid hormones again bind with
intracellular proteins with T4 binding more
strongly than T3
▪ They are again stored in the target tissues
and are used slowly over a period of days or
weeks
▪ When being used, thyroid hormones bind to
intracellular receptors, but before binding,
almost all of the thyroxine is converted to
triiodothyronine
▪ About 90 percent of the thyroid hormones
that bind with intracellular receptors is
triiodothyronine and only 10 percent is
thyroxine
▪ Thyroid hormone-receptor complex enter
the nucleus and then bind to hormone-
response elements in DNA to initiate
transcription of large number of genes
FUNCTIONS OF THYROID HORMONES
▪ Thyroid hormones increase transcription of
large numbers of genes
▪ Increase basal metabolic rate to 60 to 100
percent above normal
 ▪ Rate of food utilization for energy is greatly
accelerated, hence, increased appetite
▪ Increase protein synthesis and protein
catabolism
▪ Increase the number and activity of
mitochondria, which in turn increase the
rate of ATP formation
▪ Increase active transport of ions through
cell membrane, especially the sodium-
potassium pump
▪ Promote growth and development of the
brain during fetal life and for the first few
years of postnatal life
▪ Growth rate of young people is greatly
increased
▪ Effect on vitamin metabolism – increased
need for vitamins because of increased
quantities of enzymes
▪ Effect on body weight – greatly increased
thyroid hormone almost always decreases
body weight and greatly decreased almost
always increases the body weight
▪ Effect on cardiovascular system
▪ Increase in blood flow and cardiac
output
▪ Positive chronotropic and inotropic
effect
▪ Slightly increase in blood volume due to
vasodilation
▪ Elevated systolic pressure and reduced
diastolic pressure
REGULATION OF THYROID HORMONE SECRETION
▪ Effect on the central nervous system (CNS)
▪ Increases the rapidity of cerebration
but also often dissociates this
▪ Lack of thyroid hormone decreases
cerebration
▪ A hyperthyroid is likely to have extreme
nervousness and many psychoneurotic
tendencies (anxiety, extreme worry,
paranoia)
▪ Effect on the function of the muscles
▪ Increase in thyroid hormone usually
makes the muscles react with vigor, but
when excessive, muscles become
weakened due to excessive protein
catabolism
▪ On the other hand, lack of thyroid
hormone causes the muscles to become
sluggish and they relax slowly after
contraction
▪ Fine muscle tremor (10 to 15 times per
second)
▪ Tremor is an important means of
assessing the degree of thyroid
hormone effect on the CNS
▪ Effect on sleep
▪ Because of exhausting effect on
musculature and CNS, a hyperthyroid
has a feeling of constant tiredness, but
because of the excitable effects of
thyroid hormones on synapses, it is
difficult to sleep
▪ On the other hand, extreme
somnolence is a characteristic of
hypothyroidism, with sleep lasting 12 to
14 hours a day
▪ Effect on other endocrine glands – increased
thyroid hormone increases the rates of
secretion of most other endocrine glands, but
also increases the need of the tissues for the
hormones
▪ Effect on sexual function
▪ In men, great excesses of hormone
frequently cause impotence, but lack of
hormone is likely to cause loss of libido
▪ In women, lack of thyroid hormone
often causes menorrhagia and
polymenorrhea
▪ Thyroid hormone secretion is regulated by
hormones from the hypothalamus and the
anterior pituitary gland
▪ The hypothalamus secretes thyrotropin-
releasing hormone (TRH), which travels to the
anterior pituitary gland and stimulates the
secretion of thyroid-stimulating hormone (TSH)
▪ In turn, TSH stimulates the secretion of thyroid
hormones from the thyroid gland
▪ Increasing blood levels of TSH increase the
synthesis and release of thyroid hormones from
thyroglobulin while decreasing blood levels of
TSH decreases the synthesis and release of
thyroid hormones
▪ The result is both an immediate increase in the
secretion of thyroid hormones and prolonged
growth of the thyroid glandular tissue
▪ Thyroid hormones have a negative-feedback
effect on the hypothalamus and anterior
 pituitary, so that increasing levels of thyroid
hormones inhibit the secretion of TRH and TSH
▪ Because of the negative-feedback effect,
thyroid hormones fluctuate within a narrow
concentration range in the blood
ABNORMAL THYROID HORMONE SECRETION
▪ A loss of negative feedback will result in excess
TSH, which causes the thyroid gland to enlarge,
a condition called goiter
▪ One type of goiter, called endemic goiter,
develops if iodine in the diet is too low
▪ As less thyroid hormone is synthesized and
secreted, TRH and TSH secretions increase
above normal levels and cause dramatic
enlargement of the thyroid gland
▪ Without normal rate of thyroid hormone
secretion, growth and development cannot
proceed normally
▪ Lack of thyroid hormone is called
hypothyroidism
▪ In infants, hypothyroidism can result in
cretinism, characterized by mental retardation,
short stature, and abnormally formed skeletal
structures
▪ In adults, hypothyroidism results in decreased
BMR, sluggishness, reduced ability to perform
routine tasks, and myxedema
▪ An elevated rate of thyroid hormone secretion,
known as hyperthyroidism, causes an increased
BMR, extreme nervousness, and chronic fatigue
▪ Graves’ disease is a type of hyperthyroidism
that results when the immune system produces
abnormal proteins, called thyroid-stimulating
immunoglobulin (TSI), that are similar in
structure and function to TSH
▪ Graves’ disease is often accompanied by bulging
of the eyes, a condition called exophthalmia
CALCITONIN
▪ In addition to thyroid hormones, the
parafollicular cells or C cells of the thyroid gland
secrete calcitonin, which is secreted if blood
concentration of calcium ion becomes too high
▪ Calcitonin causes Ca2+ levels to decrease to their
normal range
▪ Refer to Chapter 5-4: Bone and Calcium
Homeostasis
PARATHYROID GLAND SECTION 13-3
▪ Four tiny parathyroid glands are embedded in
the posterior wall of the thyroid gland
▪ The chief cells of the parathyroid gland secrete
a hormone called parathyroid hormone (PTH),
which is essential for the regulation of blood
calcium levels
▪ PTH is more important than calcitonin in
regulating blood Ca2+ levels
▪ Refer to Chapter 5-4: Bone and Calcium
Homeostasis
PATHOPHYSIOLOGY
Abnormalities in PTH Secretion and Calcium
Metabolism
▪ Rickets
▪ Osteomalacia
▪ Osteoporosis
▪ Hypoparathyroidism
▪ Hyperparathyroidism
ADRENAL GLANDS SECTION 13-4
▪ The adrenal glands are two small glands located
at the superior pole of the kidneys
▪ Each adrenal gland has an inner part, called the
adrenal medulla, and an outer part, called the
adrenal cortex
▪ The adrenal medulla and the adrenal cortex
function as separate endocrine glands
HORMONES OF THE ADRENAL MEDULLA
▪ The adrenal medulla, the central 20 percent
of the adrenal gland, is functionally related
to the sympathetic nervous system
▪ The principal hormone released from the
adrenal medulla is epinephrine, or
adrenaline, although small amounts of
norepinephrine are also released
▪ The adrenal medulla releases these
hormones in response to stimulation by the
sympathetic nervous system, which
becomes most active when a person is
excited or physically active
▪ These hormones bind to membrane-bound
receptors in their target tissues
 ▪ Stress and low blood glucose levels can also as important to body function as their
increase sympathetic stimulation of the effects on carbohydrate metabolism
adrenal medulla
▪ Small amounts of sex hormones are
▪ Epinephrine and norepinephrine are
secreted, especially androgenic hormones,
referred to fight-or-flight hormones
which exhibit about the same effects in the
because of their role in preparing the body
body as the male sex hormone
for vigorous physical activity
testosterone
Major Effects of Epinephrine and Norepinephrine
▪ Androgenic hormones are normally of only
1. Increased breakdown of glycogen to slight importance, although in certain
glucose in the liver abnormalities of the adrenal cortex,
2. Increased release of glucose into the extreme quantities can be secreted and can
blood then result in masculinizing effects
3. Increased mobilization of free fatty
▪ More than 30 steroids have been isolated
acids from adipose tissue
from the adrenal cortex, but only two are of
4. Positive chronotropic effect, which
exceptional importance to the normal
causes blood pressure to rise
endocrine function of the human body:
5. Stimulation of smooth muscle in walls
of arteries supplying the internal organs o Aldosterone, which is the principal
and the skin, but not those supplying mineralocorticoid, and accounts for
the skeletal muscle about 90 percent of all
6. Blood flow to internal organs and the mineralocorticoid activity
skin decreases, as do the functions of
o Cortisol, which is the principal
internal organs, but blood flow through
glucocorticoid, and accounts for
skeletal muscles increases
about 95 percent of all
7. Increased blood pressure due to
glucocorticoid activity
smooth muscle contraction in walls of
blood vessels in internal organs and the Transport and Fate of Adrenal Cortex Hormones
skin
▪ Cortisol binds in the blood mainly with a
8. Increased metabolic rate of several
globulin called cortisol-binding globulin, or
tissues, especially skeletal muscle,
transcortin, and to a lesser extent with
cardiac muscle, and nervous tissue
albumin
HORMONES OF THE ADRENAL CORTEX ▪ About 95 percent of cortisol is normally
transported in the bound form and about 6
▪ Adrenal cortex secretes an entirely different
percent is free
group of hormones called corticosteroids –
▪ Aldosterone combines only loosely with
mineralocorticoids, glucocorticoids, and
plasma protein so that about 50 percent is
androgens
in the free form
▪ These hormones are all synthesized from
▪ The hormones become fixed in the target
the steroid cholesterol, and they all have
tissues or destroyed within 1 to 2 hours for
similar chemical formulas
cortisol and within about 30 minutes for
▪ However, slight differences in their
aldosterone
molecular structures give them several very
▪ Adrenal steroids are degraded mainly in the
different but very important functions
liver
▪ Mineralocorticoids have gained this name
▪ About 25 are excreted in the bile and then
because they especially affect the
in the feces and the remaining 75 percent in
electrolytes of the extracellular fluids –
the urine
sodium and potassium, in particular
▪ Normal concentration of aldosterone in
▪ Glucocorticoids have gained their name blood is about 6 nanograms per deciliter,
because they exhibit an important effect in and the secretory rate is 150 to 250 µg/day
increasing blood glucose concentration ▪ The concentration of cortisol in blood
averages 12 µg/dL, and the secretory rate
▪ Glucocorticoids also have additional effects
averages 15 to 20 mg/day
on both protein and fat metabolism that are
Functions of Mineralocorticoids – Aldosterone
▪ Total loss of adrenocortical secretion usually
causes death within 3 days to 2 weeks unless
the person receives salt therapy or injection of
mineralocorticoids
▪ Without mineralocorticoids:
▪ K+ concentration in ECF rises markedly
▪ Na+ and Cl- concentrations in ECF
decrease
▪ Total ECF volume and blood volume
become greatly reduced
▪ The person soon develops diminished
cardiac output, which proceeds to a
shock-like state followed by death
▪ Although aldosterone accounts for
nearly 90 percent of the
mineralocorticoid activity of the
corticosteroids, cortisol also provides a
significant mineralocorticoid activity
▪ Although the mineralocorticoid activity
of cortisol is only 1/400 that of
aldosterone, it is secreted about 80
times as much as aldosterone
▪ Effect on renal tubular reabsorption of sodium
and renal tubular secretion of potassium
▪ Increased absorption of sodium and
simultaneous excretion of potassium
by the renal tubular epithelial cells,
especially in the collecting tubule and to
a lesser extent in the distal tubule and
collecting duct
▪ Aldosterone conserves sodium in the
expense of potassium
▪ Effect on ECF volume and arterial pressure
▪ Even though aldosterone has a potent
effect in decreasing the rate of sodium
ion excretion by the kidneys, the
concentration of sodium in ECF rises
very little
▪ This is because when Na+ is reabsorbed
by the renal tubules, there is
simultaneous osmotic absorption of
almost equivalent amounts of water
▪ Therefore, ECF volume increases but
without much change in Na+
concentration
▪ Excess aldosterone causes hypokalemia and
muscle weakness while too little aldosterone
causes hyperkalemia and cardiac toxicity,
inevitably leading to cardiac failure
▪ Effect of aldosterone on increasing renal
tubular hydrogen ion secretion, resulting in mild
alkalosis – increased tubular secretion of
hydrogen ions in exchange for sodium (Na+/H+
antiport)
▪ Aldosterone greatly increases the reabsorption
of Na+ and Cl- and the secretion of K+ by the
ducts of sweat glands and salivary glands
▪ Aldosterone also greatly enhances Na+
absorption by the intestines, especially in the
colon, which prevents loss of Na+ in the stools
▪ In the absence of aldosterone, sodium
absorption in the intestines is poor, leading to
failure to absorb chloride, other anions, and
water – the unabsorbed Na+ and Cl- as well as
water then lead to diarrhea, with further loss of
salt from the body
Regulation of Aldosterone Secretion
1. Increased K+ concentration in the ECF greatly
increases aldosterone secretion (most potent
stimuli)
2. Increased activity of the renin-angiotensin
system also greatly increases aldosterone
secretion (most potent stimuli)
3. Increased Na+ concentration in the ECF very
slightly decreases aldosterone secretion
4. ACTH from the anterior pituitary gland is
necessary for aldosterone secretion but has
little effect in controlling the rate of secretion
Functions of Glucocorticoids
▪ At least 95 percent of glucocorticoid activity
results from secretion of cortisol, also known as
hydrocortisone
▪ In addition to this, a small but significant
amount of glucocorticoid activity is provided by
corticosterone
▪ Effects of cortisol on carbohydrate metabolism
– elevates blood glucose concentration and
causes adrenal diabetes
▪ Effects of cortisol on protein metabolism -
reduction in cellular protein of all body cells
except the liver via decreased protein synthesis
and increased protein catabolism
▪ Effects of cortisol on fat metabolism – increased
use of fatty acids for energy, which is an
important factor for long-term conservation of
body glucose and glycogen
▪ Almost any type of stress, whether physical or
neurogenic, will cause an immediate and
marked increase in ACTH secretion by the
 anterior pituitary gland, followed within
minutes by greatly increased cortisol secretion
▪ Anti-inflammatory effects of cortisol through
two mechanisms:
1. Blocking the early stages of
inflammation process before
inflammation even begins, or;
2. If inflammation has already begun, it
causes rapid resolution of inflammation
and increased rapidity of healing
▪ Effect on allergy
▪ Cortisol blocks the inflammatory
response to allergic reactions
▪ But cortisol does not prevent the basic
allergic reaction between antigen and
antibody
▪ Effect on blood cells and on immunity in
infectious diseases
▪ Cortisol decreases the number of
eosinophils and lymphocytes in blood
▪ Disadvantage: Level of immunity for
almost all foreign invaders of the body
is decreased
▪ Advantage - useful in preventing
rejection of transplanted organs
▪ By some unknown mechanism, cortisol
increases the production of red blood
cells
Regulation of Cortisol Secretion
▪ Almost no stimuli have direct control effects on
the adrenal cells that secrete cortisol
▪ Instead, secretion of cortisol is controlled
almost entirely by ACTH (corticotropin or
adrenocorticotropin) secreted by the anterior
pituitary gland
▪ ACTH also enhances production of adrenal
androgens
▪ ACTH is a large polypeptide, containing 39
amino acids
▪ Mechanism by which ACTH activates
adrenocortical cells to produce steroids is by
binding to membrane-bound receptors of
adrenocortical cells
▪ Control of ACTH secretion is performed by the
hypothalamus through the secretion of
corticotropin-releasing hormone or factor (CRH
or CRF), a peptide containing 41 amino acids
Abnormalities of Adrenocortical Secretion
▪ Hypoadrenalism – Addison’s disease
▪ Mineralocorticoid deficiency
▪ Glucocorticoid deficiency
▪ Melanin pigmentation of the mucous
membranes and skin – uneven melanin
deposition, occasionally in blotches
▪ Addisonian crisis – a condition where there is a
critical need for extra glucocorticoids due to
associated severe debility in times of stress
▪ Hyperadrenalism – Cushing’s syndrome
▪ Hypersecretion by the adrenal cortex
often causes a complex of hormonal
effects called Cushing’s disease
▪ Results from either a cortisol-secreting
tumor of one adrenal cortex or general
hyperplasia of both adrenal cortices
due to ectopic secretion by ACTH by a
tumor elsewhere in the body, such as
an abdominal carcinoma
▪ Moon facies, buffalo-hump
▪ Primary Aldosteronism
▪ Adrenogenital syndrome
PANCREAS SECTION 13-5
▪ The pancreas is composed of two major types
of tissues:
o Acini, which secrete digestive juices
into the duodenum (exocrine portion)
o Islets of Langerhans, which is the
endocrine part of the gland and are
dispersed throughout the acini
▪ A human pancreas has 1 to 2 million islets of
Langerhans, each organized around capillaries
into which its cells secrete their hormones
▪ Three major types of cells in the islets of
Langerhans
o Beta cells, constituting about 60
percent of all the cells, lie mainly in the
middle of the islet and secrete insulin
o Alpha cells, about 25 percent of the
total, secrete glucagon
o Delta cells, about 10 percent of the
total, secrete somatostatin
o In addition, at least one other type of
cell, the PP cell, is present in small
numbers in the islets and secretes a
hormone of uncertain function called
pancreatic polypeptide
 ▪ The close interaction among these cell types in
the islets of Langerhans allow direct control of
secretion of some of the hormones by the other
hormones
▪ For instance, insulin inhibits glucagon secretion,
and somatostatin inhibits the secretion of both
insulin and glucagon
INSULIN AND ITS METABOLIC EFFECTS
▪ Insulin was first isolated from the pancreas in
1942 by Banting and Best
▪ Profound effects on carbohydrate metabolism;
however, it is the abnormalities of fat
metabolism which cause conditions such as
acidosis and arteriosclerosis, which are usual
causes of death of a diabetic patient
▪ In patients with prolonged diabetes, diminished
ability to synthesize proteins leads to wasting of
tissues as well as many cellular disorders
▪ Therefore, it is clear that insulin affects fat and
protein metabolism almost as much as it does
carbohydrate metabolism
▪ Insulin is a hormone associated with energy
abundance
▪ When there is abundance of energy-giving food
in the diet, especially excess amounts of
carbohydrates and proteins, insulin is secreted
in great quantity
▪ This is especially true for excess carbohydrates,
less for excess proteins, but only slightly even
for fats
▪ Plays an important role in storing the excess
energy substances
o Excess carbohydrates stored as
glycogen mainly in the liver and muscles
o Causes fat storage in adipose tissue
o Excess carbohydrates that cannot be
stored as glycogen are converted into
fats and also stored in adipose tissue
o In the case of proteins, it has direct
effect in promoting amino acid uptake
by cells and conversion of these amino
acids into protein
o In addition, it inhibits the breakdown of
proteins that are already in the cells
CHEMISTRY OF INSULIN
▪ Human insulin, a small protein, has a molecular
weight of 5808
▪ It is composed of two amino acid chains,
connected to each other by disulfide linkages
▪ It is synthesized by the beta cells of the
pancreas through the usual cell machinery for
protein synthesis
▪ The insulin mRNA produced from transcription
of the insulin gene attaches to the ribosomes of
rough ER for translation to form an insulin
preprohormone (MW 11,500)
▪ This initial preprohormone is then cleaved in
the rough ER to form proinsulin (MW 9000),
which is then further cleaved in the Golgi
apparatus to insulin before being packaged in
the secretory granules
▪ However, about one sixth of the final secreted
product is still in the form of proinsulin, which
has virtually no insulin activity
▪ In the blood, insulin circulates almost entirely in
an unbound form
▪ It has a plasma half-life that averages only
about 6 minutes, so that it is mainly cleared
from the circulation within 10 to 15 minutes
▪ Degraded by the enzyme insulinase mainly in
the liver, to a lesser extent in the kidneys and
muscle, and slightly in most other tissues
ACTIONS OF INSULIN
Activation of Target Cell Receptors by Insulin
▪ Within seconds after insulin binds to its
receptor, the membrane of about 80
percent of the body’s cells (especially of
muscle and adipose cells, but not true of
most neurons in the brain) become highly
permeable to glucose
▪ In addition, the cell membrane becomes
more permeable for many of the amino
acids, potassium ions, and phosphate ions
▪ Slower effects occur during the next 10 to
15 minutes to change the activity levels of
many intracellular metabolic enzymes
▪ Much slower effects continue to occur for
hours and even several days as a result
from changed rates of translation of
messenger RNA at the ribosomes to form
new proteins and still slower effects from
changed rates of transcription of DNA in the
cell nucleus
Effect of Insulin on Metabolism
▪ Immediately after a high-carbohydrate meal,
glucose that is absorbed into the blood causes
rapid secretion of insulin, which, in turn, causes
rapid uptake, storage, and use of glucose by
 almost all tissues of the body, but especially by
the muscles, adipose tissue, and liver
▪ Increases the utilization of glucose by most of
the body’s tissues, which automatically
decreases the utilization of fat, thus
functioning as a “fat sparer”
▪ Promotes protein formation and prevents
protein degradation, thus functioning as a
“protein sparer”
Effect of Insulin on Growth
▪ Synergistic effect with growth hormone
▪ Administration of either growth hormone or
insulin one at a time causes almost no growth
▪ A combination of these hormones, however,
cause dramatic growth
▪ Perhaps a small part of this necessity for both
hormones results from the fact that each
promotes cellular uptake of a different selection
of amino acids, all of which are required if
growth is to be achieved
CONTROL OF INSULIN SECRETION
▪ Stimulation of insulin secretion by blood
glucose levels
▪ Amino acids, most potent of these are arginine
and lysine, strongly potentiate the glucose
stimulus for insulin secretion
▪ However, amino acids in the absence of
glucose stimulus cause only a small increase in
insulin secretion
▪ Mixture of several important GIT hormones –
gastrin, secretin, cholecystokinin, and gastric
inhibitory peptide (the most potent) - will
cause a moderate increase in insulin secretion
▪ Other hormones that either directly increase
insulin secretion or potentiate the glucose
stimulus for insulin secretion include growth
hormone, cortisol, and to lesser extent,
progesterone and estrogen
▪ Stimulation of the parasympathetic nerves to
the pancreas can increase insulin secretion
GLUCAGON AND ITS FUNCTIONS
▪ Glucagon, a hormone secreted by the alpha
cells of the islets of Langerhans when blood
glucose concentration falls, has several
functions that are opposed to those of insulin
▪ Most important of these functions is to increase
the blood glucose concentration
▪ Large polypeptide with a MW of 3485 and is
composed of a chain of 29 amino acids
▪ Hyperglycemic hormone
▪ Glucagon in very abnormally large
concentrations also:
1. Enhances the strength of the heart
2. Enhances bile secretion
3. Inhibits gastric acid secretion
CONTROL OF GLUCAGON SECRETION
▪ Increased blood glucose inhibits glucagon
secretion
▪ High concentrations of amino acids in the
blood, especially after a protein meal, stimulate
glucagon secretion – in this instance, glucagon
and insulin responses are not opposites
▪ In exhaustive exercise, the blood concentration
of glucagon often increases fourfold to fivefold
SOMATOSTATIN
▪ The delta cells of the islets of Langerhans
secrete the hormone somatostatin, a
polypeptide containing only 14 amino acids that
has an extremely short half-life in the
circulating blood of only 3 minutes
▪ Factors related to ingestion of food stimulate
somatostatin secretion:
1. Increased blood glucose
2. Increased amino acids
3. Increased fatty acids
4. Increased concentrations of several GIT
hormones released from the upper GIT
in response to food intake
▪ In turn, somatostatin has the following
inhibitory effects:
1. Acts locally within the islets of
Langerhans to depress secretion of both
insulin and glucagon
2. Decreases the motility of the stomach,
duodenum, and gallbladder
3. Decreases both secretion and
absorption in the GIT
▪ It has been suggested that the principal role of
somatostatin is to:
1. Extend the period of time over
which food nutrients are
assimilated into the blood
2. At the same time, the effect of
somatostatin to depress insulin and
glucagon secretion decreases the
utilization of absorbed nutrients by
tissues, thus preventing rapid
 exhaustion of food and therefore
making it valuable over a long
period of time

▪ Somatostatin is also known as growth hormone

inhibitory hormone, which is secreted by the
hypothalamus to suppress secretion of growth
hormone by the anterior pituitary gland