Endocrinology
Major endocrine glands in the body
MODES OF HORMONE DELIVERY I:

ENDOCRINE:


Most common (classical) mode, hormones
delivered to target cells by blood.
PARACRINE:
Hormone released diffuses to its target cells
through immediate extracellular space.
 Blood is not directly involved in the delivery.

MODES OF HORMONE DELIVERY II:

NEUROENDOCRINE:


Hormone is produced and released by a neuron,
delivered to target cells by blood.
AUTOCRINE:

Hormone released feeds-back on the cell of origin,
again without entering blood circulation.
HORMONE-TARGET CELL
SPECIFICITY

Only target cells, or cells that have specific
receptors, will respond to the hormone’s
presence.

The strength of this response will depend on:
Blood levels of the hormone
 The relative numbers of receptors for that hormone on or
in the target cells
 The affinity (or strength of interactions) of the hormone
and the receptor.

HALF-LIFE, ONSET, and
DURATION of HORMONE
ACTIVITY


The affinity of hormones to their specific
receptors is typically very high
The actual concentration of a circulating
hormone in blood at any time reflects:
Its rate of release.
 The speed of its inactivation and removal from the
body.

Half-life

The half-life is the time required for the hormone to
loose half of its original effectiveness (or drop to half of
its original concentration.

General rule: 10 half-lives is the time it takes to completely
clear the original compound from the system.
Half-life
100
90
80
70
60
50
Series1
40
30
20
10
0
0
1
2
3
4
5
6
7
8
Onset of activity

The time required for hormone effects to take
place varies greatly, from almost immediate
responses to hours or even days.

In addition, some hormones are produced in an
inactive form and must be activated in the target
cells before exerting cellular responses.

In terms of the duration of hormone action, it
ranges from about 20 minutes to several hours,
depending on the hormone.
CONTROL OF HORMONE RELEASE:



The synthesis and secretion of most hormones are
usually regulated by negative feedback systems.
As hormone levels rise, they stimulate target organ
responses. These in turn, inhibit further hormone
release.
The stimuli that induce endocrine glands to synthesize
and release hormones belong to one of the following
major types:



Humoral
Neural
Hormonal
CHEMISTRY OF HORMONES




Peptide hormones: largest, most complex, and most
common hormones. Examples include insulin and prolactin
Steroid hormones: lipid soluble molecules synthesized from
cholesterol. Examples include gonadal steroids (e.g
testosterone and estrogen) and adrenocortical steroids (e.g.
cortisol and aldosterone).
Amines: small molecules derived from individual amino
acids. Include catecholamines (e.g. epinephrine produced by
the adrenal medulla), and thyroid hormones.
Eicosanoids: small molecules synthesized from fatty acid
substrates (e.g. arachidonic acid) located within cell
membranes
Transforming growth factor – b (TGF-b) receptor
• An important
serine-theronine
kinase receptor
enzyme
• Involved in
regulating many
cellular processes
• Malfunctions result
in many diseases
including Cancer,
atherosclerosis etc.
Figure 4.18b
Cyclic-AMP Signaling
Figure 3.27
Pituitary Gland
Hormones of the anterior pituitary

There are 6 main hormones which are secreted by the
adenohypophysis:

1) Growth hormone (also known as somatotropin).

2) Thyroid-stimulating hormone (also known as thyrotropin).

3) Adrenocorticotropic hormone (also known as corticotropin).

4) Prolactin.

5) Follicle-stimulating hormone.

6) Luteinizing hormone.
Control of pituitary gland secretion


Secretion of each hormone by the
adenohypophysis is controlled by
neurohormones secreted by nerves in the
hypothalamus.
In most cases there are two neurohormones
controlling the secretion of a pituitary hormone.
One which stimulates pituitary secretion and one
which inhibits pituitary secretion.
Neurohormones:



Are hormones secreted by nerve cells. These are
true hormones, since they are secreted into the
bloodstream.
All are secreted by neurosecretory neurons in
the hypothalamus.
They are secreted into the hypophyseal portal
system, which then carries the blood to the
anterior pituitary.
Pituitary portal system





Arterioles break into capillaries in the hypothalamus.
The axons of the neurosecretory cells form plexuses
with these capillaries.
Downstream, the capillaries combine into a vein which
carries the blood to the pars distalis.
The vein breaks into a capillary network which supplies
all the cells of the anterior lobe.
Thus, the neurohormones are carried directly (well, sort
of) from the hypothalamus to the adenohypophysis.
Growth hormone (GH)

Growth hormone is secreted by somatotrophs.

GH is a protein hormone consisting of a single peptide chain of
191 amino acids.

GH secretion is stimulated by the secretion of Growth Hormone
Releasing Hormone (GHRH) by the hypothalamus.

GH secretion is inhibited by the secretion of somatostatin by the
hypothalamus.

GH activates a tyrosine kinase receptor.
Functions of GH:

GH has effects of every cell of the body, either directly
or indirectly. Primarily, it decreases the uptake and
metabolism of glucose. (Elevates plasma glucose)

Increases the breakdown of fat. (Increases the blood
levels of fatty acids)

Increases the uptake of amino acids from the blood and
increases protein synthesis in cell. (Decreases plasma
amino acids)
Actions of GH on specific cell types:

Muscle cells:

Increases amino acid uptake
Increases protein synthesis
Decreases glucose uptake



Net result: Increased Lean body mass

Chondrocytes:

increases uptake of sulfur
increases
 increases
 increases
 increases
 increases
 increases


chondroitin sulfate production
DNA, RNA synthesis
Protein synthesis
Amino acid uptake
Collagen synthesis
Cell size and number
Net result: Increased Linear growth

Hepatocytes:

Stimulates the production of somatomedins by
the liver.

These somatomedins directly regulate metabolic
function in target cells. They are also called
insulin-like growth factors, or IGFs.

Adipocytes:

Decreases glucose uptake
Increases lypolysis


Net result: Decreased Adiposity

Other cell types in general:
Increased protein synthesis
 Increased DNA, RNA synthesis
 Increased cell size and number



Net result: Increased organ size
Increased organ function
Other considerations:

GH has a short half-life of about 20 minutes.
However, the IGFs are much longer lived (T1/2
of about 20 hours).
GH and Insulin actions are correlated:

When there is ample dietary intake of proteins and carbohydrates,
then amino acids can be used for protein synthesis and growth.

Under these conditions, both insulin and GH secretion are
stimulated.


Net result: Amino acids are shunted to protein synthesis and glucose is shunted
to metabolism.
However, under conditions where only carbohydrates are ingested,
insulin secretion is increased, but GH secretion is decreased.

Net result: Both glucose AND amino acids are shunted to metabolism.
Pathophysiology of abnormal GH
secretion:

Hyposecretion:

Pre-adolescents:


Decreased GH secretion (or sensitivity) results in slow
growth and delayed onset of sexual maturation. These
children also tend to be slightly chubby.
Post-adolescents:

Generally, no serious problems are associated with
hyposecretion of GH in mature individuals. However, in
very severe cases there can be progeria (rapid and premature
aging).
Hypersecretion:

Pre-adolescents: (before closure of
epiphyseal plates)

Hypersecretion results in gigantism, where
affected individuals grow extremely rapidly and
become abnormally tall (even over 2.4 m). Body
proportions remain relatively normal. Usually,
there are cardiovascular complications later in
life.

Post- adolescents: (after epiphyseal closure).

Hypersecretion results in tissue enlargement.
This is particularly true of the bones, which get
heavier and thicker. They cannot elongate since
the epiphyseal plates are closed. A common
symptom is a coarsening of the facial features
and enlargement of the hands and feet. This
condition is known as acromegaly.
Treatments of GH secretion disorders:

Hypersecretion is usually caused by a tumour in
the pituitary gland. Treatment consists of
surgical or radiation ablation of the tumour
mass.

Hyposecretion is usually treated in children by
hormone replacement therapy. This is generally
not required in adults, unless GH secretion is
completely abolished.
Prolactin (PRL)

Structurally, very similar to growth hormone
(single peptide chain of 198 amino acids).

PRL is secreted by mammotrophs (also referred
to as lactotrophs).

Secretion of PRL is also under dual control by
the hypothalamus.

Primarily under inhibitory control. This means that if
there is an injury to the hypophyseal portal system
which blocks hypothalamic regulation of the pituitary
gland, PRL levels increase. All other pituitary hormone
levels decrease when this happens.

Dopamine is secreted by neuroendocrine cells in the
hypothalamus and inhibits PRL release.

PRL release is stimulated by thyrotropin releasing
hormone (TRH), vasoactive intestinal peptide (VIP)
and at least one other as yet unidentified factor.

PRL activates a tyrosine kinase receptor.
Functions of PRL:

In humans, the only effects of PRL so far
identified are on reproduction and nursing.

PRL is important in stimulating differentiation of
breast tissue during development.

Stimulates further development of mammary
glands during pregnancy.

Stimulates milk production (lactation) after pregnancy.

PRL has a role in regulation of the female reproductive
cycle. However, its precise role has not been delineated
yet. Excess PRL secretion is known to block synthesis
and release of gonadotropins, disrupting menstruation
and causing infertility.

PRL also can regulate male fertility, but how it does so
remains unclear.
Pathophysiology of PRL secretion:

Hyposecretion is never seen. However,
hyperprolactinemia (excess secretion of PRL) is
a fairly common disorder. Symptoms in women
usually include amenorrhea (cessation of
menstruation), galactorrhea (abnormal lactation)
and infertility. In men, infertility and
galactorrhea are the most common symptoms.

Treatment usually consists of administration of a
dopaminergic agonist, such as bromocriptine.
Thyroid Stimulating hormone (TSH)

TSH is a glycoprotein hormone composed of 2
peptide chains a and b.

The a subunit is called “unspecific” because it is
also incorporated into two other unrelated
pituitary hormones (LH and FSH).

The b subunit contains the biologically active
sites. However, it must be combined with the a
subunit in order for the hormone to be active.

TSH secretion is controlled very tightly by the
hypothalamus.

TSH secretion is stimulated by Thyrotropinreleasing hormone (TRH). TRH is a tripeptide,
meaning it is composed of three amino acids.

TRH secretion is stimulated by thermal and
caloric signals in the brain.
Control of TSH secretion

Negative control of TSH secretion occurs in two
ways:

Triiodothyronien or T3 (which will be discussed
later) feeds back on the hypothalamus to stimulate
secretion of dopamine and somatostatin. These two
factors both function as TSH-release inhibiting
factors.

T3 can feed back directly onto the thyrotrophs to
directly inhibit TSH secretion.
Function of TSH:

TSH stimulates the follicular cells of the thyroid
to induce a number of responses:

TSH activates both the cAMP and PIP pathways:



Increased cAMP
Increased [Ca2+]i
TSH can stimulate both cell growth (of follicular
cells) and secretion of T3 and thyroxine ( T4 ).
Adrenocorticotropic hormone (ACTH)

ACTH is a single peptide chain which is
relatively small (30 amino acids).

ACTH secretion is primarily under stimulatory
control (i.e. there isn’t an ACTH-release
inhibitory factor).

ACTH secretion is stimulated by corticotropin
releasing hormone (CRH).

CRH secretion can be stimulated by a large
number of factors, most of which would be
considered stress factors.

Examples; infection, trauma, sleep cycle, anxiety,
depression and others. (Just remember stress).
Functions of ACTH:

ACTH stimulates the adrenal gland to secrete cortisol.

ACTH levels are associated with the sleep cycle.

ACTH stimulates the cAMP pathway in adrenocorticol
cells.

ACTH can directly inhibit CRH secretion (negative
feedback).
Follicular-Stimulating hormone (FSH)
Luteinizing Hormone (LH)

These are generally grouped together and called gonadotropines.

Gonadotropins are secreted by the gonadotrophs, which
synthesize and secrete both LH and FSH.

Both LH and FSH are peptide hormones.

Secretion of gonadotropins is mainly under positive control.

Hypothalamus secretes gonadotropin-releasing hormone
(GnRH) which stimulates gonadotrophs to secrete both LH and
FSH.
Functions of LH and FSH:

LH and FSH stimulate secretion of the sex steroids by the
gonads. Mainly estrogen in women and testosterone in men.

FSH also stimulates gonadal release of inhibin, which serves as a
negative feedback factor to block release of FSH by pituitary.

LH and FSH stimulate the gonadal release of activin, which can
have positive feedback on gonadotropin secretion by the
pituitary.

Gonadal secretion of estrogen and testosterone can negatively
feedback on both the hypothalamus, to reduce GnRH secretion,
and the gonadotrophs directly, to reduce gonadotropin
secretions.
Hormones of the posterior pituitary:

Remember that the neurohypophysis serves as a storage organ
for hormones produced by neurosecretory cells in the
hypothalamus.

There are two hormones secreted by the neurohypophysis:


1) antidiuretic hormone (ADH)
2) oxytocin

Both hormones are peptide hormones containing 9 amino acid
residues.

They differ in only 2 amino acids, but have very different
functions.
ADH

Term: diuresis ö means production of urine.

ADH inhibits urine production, i.e. conserves water in the body.

Main target for ADH are the cells in the kidney which reabsorb
water (will be covered in detail in the section on renal
physiology).

ADH secretion is stimulated by either an increase in the osmotic
concentration of the blood, or by a decrease in blood volume

usually sensed by a decrease in blood pressure.



Secretion of ADH causes retention of water, which will
tend to counteract both an increase in blood
concentration and/or decrease in blood volume.
cannot overcome serious blood loss.
Conversely, excess consumption of water will have two
effects:



increase blood volume (and pressure).
decrease blood concentration.
Under these conditions ADH secretion is inhibited.


This results in formation of more urine, which is usually fairly
dilute.
Blood loses water and thus volume.
Oxytocin

Release of oxytocin is under neural control (like
with ADH).

However, unlike ADH, the release of oxytocin is
largely controlled by emotional state.

Oxytocin specifically stimulates certain smooth
muscles to contract.

Primarily those of the reproductive tract and mammary
glands.

Oxytocin is required for nursing.

Principally know as the “milk letdown factor”.

It is secreted within seconds of the onset of suckling.
Sensory receptors in the nipples generate afferent
impulses that stimulate the hypothalamus, triggering
oxytocin secretion.
 Can actually be secreted in response to auditory input, i.e.
in nursing mothers in response to hearing their babies
cry.

Effects of Oxytocin

Oxytocin stimulation at low doses causes
rhythmic contractions of the uterus.

Oxytocin stimulation at high dose causes
sustained tetanic uterine contractions.

Oxytocin is often used to induce labour.

It is now generally believed that oxytocin produced by
the foetus plays a critical role in labour.

Oxytocin is also used to stop post-partum bleeding.

The number of oxytocin receptors in uterine smooth
muscles increases towards the end of pregnancy.

Oxytocin affects smooth muscle cells in uterus and
vagina of non-pregnant women.

Secretion of oxytocin during and after labour
may play an important role in the formation of
the mother-child pair-bond.

Oxytocin secreted during suckling may serve to
reinforce this pair-bond.
Oxytocin
• Peptide hormone
• Released by the posterior pituitary and by peripheral
tissues
• Oxytocin receptor is a G-protein-coupled receptor
that uses phosphatidylinositol as a second messenger
Model of oxytocin

Oxytocin secreted in response to suckling can cause
uterine contractions which may play a role in the
recovery of uterine muscle tone after pregnancy and
may serve to shrink the uterus back to normal.
Oxytocin Affects Maternal Behaviour
•
Recent studies with knock out mice has shown that oxytocin is
critical in initiating and maintaining maternal care.
•
Injecting oxytocin into the cerebral-spinal fluid of female sheep
causes them to display maternal behaviour to foreign lambs

Is required in the amygdala for social recognition

There is clear evidence that oxytocin is involved in
sexual arousal and orgasm in both men and women.


What role it plays in men is unknown. However, it may play
a strong role in reinforcing the pair-bond.
The role in women is only slightly better known.


Oxytocin is secreted in response to vaginal distention during
intercourse.
Oxytocin is also secreted in response to stimulation of the
nipples.
Oxytocin Stimulates Pair-bonding
• Since oxytocin is released during sexual arousal and orgasm in
both men and women, it is often referred to as the “the cuddle
hormone” or “the love hormone” in the popular press.
• Oxytocin is required in the amygdala for normal social
recognition.
Love and the Brain
The affected regions contain a very
high density of receptors for oxytocin
and/or vasopressin
Limbic System


Figure 7.11
A network of connected
structures that lie between
the cortex and the rest of
the brain
Influences emotions,
motivation, and memory
 Includes the thalamus and hypothalamus, and also includes:
 Amygdala – aggression, fear, interpreting facial expressions,
emotional memories.
Olfactory bulbs – integration of smell stimuli.
Hippocampus – converts short-term memory into long-term
memory
Vasopressin
• Peptide hormone
• Released by the posterior pituitary into the
blood and into the brain
• Binds to a G-protein-coupled receptor
Model of vasopressin
Thyroid Gland:

Location and Structure

The largest pure endocrine gland in the body,
located in the front of the neck, on the trachea
just below to the larynx.

Its two lobes are connected by a median tissue
mass called the isthmus.

Internally, it is composed of about 1 million of
round follicles. The walls of each follice are
formed by cuboidal and squamous epithelial
cells called follicle cells, which produce
thyroglobulin (glycoprotein).

The lumen of each follicle stores colloid, which
consists primarily of molecules of thyroglobulin.

The follicular epithelium also consists of
parafollicular cells, a separate population of
endocrine cells that produce calcitonin, a
hormone involved in calcium homeostasis.
Thyroid hormones (THs)

The two THs contain iodine and are called thyroxin or
T4 and triiodothyronine or T3.

T4 and T3 have a very similar structure as each is made
up of two tyrosine amino acids linked together and
either 4 or 3 atoms of iodine, respectively.

T4 is the main hormone produced by the thyroid and T3
has most if not all of biological activity as all target
tissues rapidly convert T4 to T3.

Except for the adult brain, spleen, testes, and the
thyroid gland itself, THs affect all other types of cells in
the body where they stimulate activity of enzymes
especially those involved in glucose metabolism

Increase metabolic rate in target tissues, which increases
body heat production (calorigenic effect).

THs also are critically important for normal growth and
development of skeletal and nervous systems and
maturation of reproductive system.
Synthesis of thyroid hormones:

Formation and storage of thyroglobulin.

This process takes place in follicle cells and the final
product is packed into vesicles, their contents are
discharged into the lumen of the follicle and become
a major part of the colloid.

Iodide trapping and oxidation to iodine.

To produce functional iodinated hormones, follicle
cells accumulate iodide from the blood. A protein
pump (iodide trap), located on the basal surface of
follicle cells, actively transports iodide into follicle
cells where it is oxidized and converted to iodine (I).

Iodination.

Once formed, iodine is attached to tyrosine amino
acids which are part of the thyroglobulin.

Iodination of one tyrosine produces
monoiodotyrosine (MIT), iodination of two
tyrosines diiodotyrosine (DIT).

Coupling.

Then enzymes within the colloid link MITs and
DITs in a highly specific fashion, as a result two
DITs linked together result in T4 , while coupling of
MIT and DIT produce T3.

Coupling (cont.)
Interactions between two DITs are more frequent so
more thyroxin.
 At this point both thyroid hormones are still
attached to thyroglobulin molecules in the colloid.


Colloid endocytosis.

Colloid droplets containing iodinated thyroglobulin
are taken up by follicle cells by endocytosis. These
combine with lysosomes to form phagolysosomes.

Cleavage of the hormones for release.

Within the phagolysosomes, the hormones are
cleaved from the thyroglobulin by lysosomal
enzymes. The free hormones then diffuse through
the basal membrane out of the follicle cell and into
the blood stream.
Transport and regulation of release:

Most released T4 and T3 immediately bind to plasma
proteins, of which the most important is thyroxinbinding globulin (TBG) produced by the liver.

Binding proteins protect T4 and T3 from immediate
degeneration by plasma enzymes, also they allow T4 and
T3 to reach target tissues, often located a significant
distance away from the thyroid gland.

Decreasing blood levels of thyroxin trigger release of
TSH from the anterior pituitary, which stimulates the
thyroid gland to produce more thyroxin.
Pathology of the thyroid gland function:

Both hypo- and hyperactivity and of the thyroid gland can cause
severe metabolic disturbances.

In adults, hypothyroidism is referred to as


myxedema.
Symptoms:


Low metabolic rate, poor resistance to cold temperatures, constipation,
dry skin (especially facial), puffy eyes, lethargy and mental sluggishness.
If hypothyroidism results from lack of iodine the thyroid gland enlarges
to form a goiter.

Severe hypothyroidism during the fetal
development and in infants is called cretinism.

Symptoms:
A short disproportionate body, a thick tongue and
neck, and mental retardation.
 The condition is preventable by thyroid hormone
replacement therapy. However, once developmental
abnormalities and mental retardation appear, they
are not reversible.

Hyperthyroidism:

The most common form of hyperthyroidism is Grave's disease, believed to be
an autoimmune disease.

The immune system produces antibodies that mimic TSH, which bind to
TSH receptors and permanently switch them on, resulting in continuous
release of thyroid hormones.

Typical symptoms include metabolic rate, sweating, rapid and irregular
heartbeat, nervousness, and weight loss despite adequate food intake.

Often, exophthalmos, or protrusion of the eyeballs, occurs caused by the
edema of tissues behind the eyes followed by fibrosis.

Treatments include surgical removal of the thyroid gland (very difficult due to
an extremely rich blood supply) or ingestion of radioactive iodine (131I), which
selectively destroys the most active thyroid cells.
Hyperthyroidism and Grave’s Disease
Parathyroid Glands:

The parathyroid glands
are small in size and are
found on the posterior
aspect of the thyroid
gland.

Typically, there are four
of them but the actual
number may vary.
Histology of the Parathyroid

The endocrine cells
within these glands
are arranged in thick,
branching cords
containing oxyphil
cells of unclear
function and most
importantly large
numbers of chief
cells that secrete
parathyroid
hormone (PTH).
PTH:

Small protein

Single most important hormone controlling calcium
homeostasis. Its release is triggered by falling blood
calcium levels and inhibited by hypercalcemia (high
blood calcium).

There are three target organs for PTH:



skeleton
kidneys
intestine
PTH stimulates the following on
these target organs:

Osteoclasts (bone absorbing cells) are stimulated to digest bone
and release ionic calcium and phosphates to the blood.

Kidneys are stimulated to reabsorb calcium and excrete
phosphate.

Intestines are stimulated to increase calcium absorption.

Vitamin D is required for absorption of calcium from ingested
food.


For vitamin D to exert this effect, it must first be converted by the
kidneys to its active form
It is this conversion that is directly stimulated by PTH.
Pathology of the parathyroid glands:

Because calcium is essential for so many
functions, including transmission of action
potentials, muscle contraction, pacemaker
activity in the heart, and blood clotting, precise
control of ionic calcium levels in body fluids is
absolutely critical. As a result both hyper- and
hypoparathyroidism can have severe
consequences.
Hyperparathyroidism:

Rare, usually the result of a parathyroid gland tumor.

Results in severe loss of calcium from the bones.

The bones soften and deform as their mineral salts are replaced
by fibrous connective tissue.

Results in hypercalcemia

Leads to, depression of the nervous system leading to abnormal reflexes
and weakness of the skeletal muscles, and formation of kidney stones as
excess calcium salts are deposited in kidney tubules.
Hypoparathyroidism:

It is a PTH deficiency, which is a common
consequence of parathyroid trauma or removal
during thyroid surgery.

The resulting hypocalcemia increases excitability
of neurons and may lead to tetany resulting in
uncontrollable muscle twitches and convulsions,
which if untreated may progress to spasms of
the larynx, respiratory paralysis and death.
ADRENAL GLANDS:

The two adrenal glands
are pyramid-shaped
organs found atop the
kidneys.

Each gland is structurally
and functionally two
endocrine glands in one.

The inner adrenal
medulla is made up of
nervous tissue and acts
as part of the
sympathetic nervous
system. The outer
adrenal cortex forms
the bulk (about 80%)
of the gland. Each of
these regions produces
its own set of
hormones.
Adrenal Medulla:

It is made up of chromaffin cells which secrete the catecholamines
epinephrine (E) (adrenaline) and norepinephrine (NE) (noradrenaline) into
the blood.

During the fight-or-flight responses, the sympathetic nervous system is
activated, including the chromaffin tissue and large amounts of
catecholamines (80% of which is E) are released.

In most cases the two hormones have very similar effects on their target
organs. However, E is the more potent stimulator of the heart rate and
strength of contraction, and metabolic activities, such as breakdown of
glycogen and release of glucose).

NE has great effect on peripheral vasoconstriction and blood pressure.
Adrenal Cortex:




The cells of the adrenal cortex are arranged in three
distinct zones, each zone producing corticosteroids.
The Zona glomerulosa is the outer-most layer of cells
and it produces mineralocorticoids, that help control
the balance of minerals and water in the blood.
The zona fasciculata is composed of cells that secrete
glucocorticoids.
The zona reticularis produce small amounts of
adrenal sex steroids.
Hormones of the Adrenal Cortex


Mineralocorticoids
Although there are several mineralocorticoids,
aldosterone is by far the most potent and accounts for
more than 95% of production. Its main function is to
maintain sodium balance by reducing excretion of this
ion from the body.

The primary target organs of aldosterone are kidney
tubules where it stimulates reabsorption of sodium ions
from urine back to the bloodstream.

Aldosterone also enhances sodium absorption from
sweat, saliva, and gastric juice.

Secretion of aldosterone is induced by a number of
factors such as high blood levels of potassium, low
blood levels of sodium, and decreasing blood volume
and pressure.

The reverse conditions inhibit secretion of aldosterone.

Glucocorticoids:

Glucocorticoids influence metabolism of most body
cells, help us resist stress, and are considered to be
absolutely essential to life.

The most important glucocorticoid in humans is cortisol, but small
amounts of cortisone and corticosterone are also produced.

The main effect of cortisol is to promote gluconeogenesis or
formation of glucose from noncarbohydrate molecules, especially
fats and proteins.

Cortisol also breaks down adipose (fat) tissue, released fatty acids
can be then used by many tissues as a source of energy and "saving"
glucose for the brain.

Blood levels of glucocorticoids increase significantly during stress,
which helps the body to negotiate the crisis.

Interestingly, chronic excess of cortisol has significant antiinflammatory and anti-immune effects and glucocorticoid drugs are
often used to control symptoms of many chronic inflammatory
disorders, such as rheumatoid arthritis or allergic responses.

Gonadocorticoids (Sex Hormones)
The amount of sex steroids produced by zona
reticularis is insignificant compared to the amounts
secreted by the gonads.
 These hormones may contribute to the onset of
puberty and the appearance of axillary and pubic hair
in both males and females.
 In adult women adrenal androgens (male sex
hormones, especially testosterone) may be, at least
partially, responsible for the sex drive.

Pathology of the adrenal cortex function:

Hyperadrenalism :



It is referred to as Cushing's disease and can be caused by a
cortisol-secreting tumour in the adrenal glands, ACTHsecreting tumour of the pituitary, or ACTH secreted by
abdominal carcinoma.
However, it most often results from the clinical
administration of pharmacological (very high) doses of
glucocorticoid drugs.
The symptoms include a persistent hyperglycaemia, dramatic
loss of muscle and bone proteins, and water and salt
retention, leading to hypertension and edema - one of its
signs is a swollen "moon" face. The only treatment is a
surgical removal of tumour or discontinuation of the drug.

Hypoadrenalism :

It is referred to as Addison's disease and involves
significant reduction in plasma glucose and sodium,
very high levels of potassium and loss of weight. The
usual treatment is corticosteroid replacement
therapy.
THE ENDOCRINE PANCREAS:

Located partially behind the stomach, the
pancreas is a mixed gland composed of both
endocrine and exocrine cells.

More than 98% of the gland is made up of
acinar cells producing an enzyme-rich juice that
enters a system of ducts and is delivered to the
duodenum of the small intestine during food
digestion.

The remaining 1-2% of cells form about 1
million of islets of Langerhans, tiny cell clusters
that produce pancreatic hormones.

The islets have four distinct populations of cells,
the two most important ones are alpha cells that
produce hormone glucagon, and more
numerous beta cells that synthesize insulin. In
addition, delta cells produce somatostatin and F
cells secrete pancreatic polypeptide (PP).
Hormones of the Pancreas:

Glucagon and insulin are directly responsible for the
regulation of blood glucose levels and their effects are
exactly opposite:

insulin is hypoglycemic (it decreases blood glucose)

glucagon is hyperglycemic (it increases blood glucose).

Pancreatic somatostatin inhibits the release of both insulin
and glucagon and slows the activity of the digestive tract.

PP regulates secretion of pancreatic digestive enzymes and
inhibits release of bile by the gallbladder.
Glucagon:

Glucagon is a 29 amino acid polypeptide with extremely potent hyperglycemic
properties. One molecule of this hormone can induce the release of 100 million
molecules of glucose into the blood.

The major target organ of glucagon is the liver, where it promotes:

Breakdown of glycogen to glucose (glycogenolysis)
Synthesis of glucose from lactic acid and from noncarbohydrate molecules such as fatty
acids and amino acids (referred to as gluconeogenesis).

Release of glucose into the blood by the liver

All these effects € blood sugar levels.

Secretion of glucagon from the alpha cells is induced by, most importantly, low blood
sugar levels but also by high amino acid levels in the blood (e.g. following a protein-rich
meal). Rising blood sugar concentration and somatostatin from the delta cells inhibit
glucagon release.

Insulin:

Insulin is a 51 amino acid protein consisting of two polypeptide chains linked
by disulfide bonds. It is synthesized as part of a larger molecule called
proinsulin and packed into secretory vesicles where its middle portion is
excised by enzymes to produce functional hormone, just before insulin is
released from the beta cell.

As mentioned earlier, insulin's main function is to lower blood sugar levels
but it also affects protein and fat metabolism.

In general, insulin:





Increases membrane transport of glucose into body cells, especially muscle and
liver cells
Inhibits the breakdown of glycogen (it should not be confused with glucagon!)
into glucose,
Increases the rate of ATP production from glucose
Increases the rate of glycogen synthesis
Increases the rate of glucose conversion to fat.

Insulin binds to tyrosine kinase receptors, but
mechanism of action, including type(s) and specific
roles of second messengers, are poorly understood.

The beta cells are stimulated to produce insulin
primarily by elevated blood sugar levels, but also by
high blood levels of amino acids and fatty acids.

Several hormones also induce the release of insulin,
including glucagon, epinephrine, growth hormone,
thyroid hormones, and glucocorticoids.

In contrast, somatostatin inhibits insulin release.