BIOC 313

Chapter 8

Hormones of Adrenal Gland

 • There are two adrenal
glands, one above each
kidney
• The outer portion of
each gland is called the
adrenal cortex

• The inner portion is

called the adrenal
medulla

• Each gland is
surrounded by a
capsule

ADRENAL
GLANDS
 Adrenal
Gland
The adrenal cortex has three
layers:
• The outer layer:
• is called the zona glomerulosa
• secretes mineralocorticoids
(mainly aldosterone)
• The middle layer:
• is called the zona fasciculata
• secretes glucocorticoids
(mainly cortisol)
• The inner layer
• is called the zona reticularis
• secretes gonadocorticoides
(sex hormones)
• The adrenal medulla is in the
center of the adrenal gland; it
secretes
• Epinephrine (80%) &
Norepinephrine (20%).
Hormones of Adrenal Cortex

• Biosynthsis
1. There is a common metabolic pathway for the biosynthesis of all steriod
hormones.The first step is the conversion of cholesterol into pregnenolone:
a) This reaction is the rate limiting step in steroidogenesis and occurs in the
mitochondria.
b) This reaction is activated by Adrenocorticotropic hormone ACTH.
c) It needs enzyme called cytochrome P-450 side chain cleavage enzyme (P-450
scc), NADPH and molecular oxygen.

2. Pregnenolone is next oxidized and then isomerized to progesterone and 17-

hydroxypregnenolone, both are further modified by series of hydroxylation and
oxidation reactions to other steroid hormones.
Biosynthsis of Hormones of Adrenal Cortex
Biosynthsis of Hormones of Adrenal Cortex

2. Pregnenolone is next oxidized and then isomerized to progesterone and 17-

hydroxypregnenolone, both are further modified by series of hydroxylation and
oxidation reactions to other steroid hormones.

3. 17-hydroxypregnenolone is converted into dehydroepiandrosterone (DHEA) which

is the main androgen produced by adrenal cortex. DHEA is then converted by DHEA
sulfotransferase (hydroxysteroid sulfotransferase 2A1, SULTA1) to DHEA sulphate,
which is then secreted in the blood.

4. The major steroid hormones secreted by the human adrenal cortex are cortisol,
corticosterone, aldosterone and DHEA sulphate.

5. Adrenal cortex can synthesize very small amount of testosterone from DHEA. Also,
small quantity of estrogens can be synthesized from aromatization of testosterone.
 1. Glucocorticoids
a) Cortisol circulates in plasma in free
form (8%) and in association of
protein (92%).
Plasma b) The free cortisol is the biologically
active form of the hormone.
Transport c) The cortisol binding protein is called
transcortin or corticosteroid binding
globulin (CBG).
d) Very small amount of cortisol is
bound to albumin.

2. Mineralocorticoids:
There is no specific plasma transport
protein, 50% of aldosterone is believed to
circulate as the free steroid in the plasma
compartment.
 1. Glucocorticoids
a) When the body is stressed,
corticotropin releasing
hormone (CRH) is released by
Regulation the hypothalamus, which
stimulates anterior pitutary to

of Adrenal b)
produce ACTH.
ACTH binds with receptors in
the cell membrane of zona
Cortical fasciculata and zona
reticularis. This leads to
Hormones activation of adenylate
cyclase and convervion of ATP
into cAMP.
c) cAMP will stimulate
formation and secretion of
glucocorticoids.
Regulation of Adrenal Glucocorticoids
Regulation of Adrenal Cortical
Hormones

2. Mineralocorticoids
a) When the body is subjected to hypotension (decreased
renal perfusion pressure), anoxia or kidney trauma, the
kidney responds by secreting renin hormone.
b) Renin will activate angiotensinogen in angiotensin I and II.
c) Angiotensin II will stimulate zona glomerularis to produce
mineralocorticoids (aldosterone) which act on distal
convulted tubules of the kidney causing Na+ and water
reabsorption and K+ excretion.
 ACE= angiotensin
converting enzyme

ACE Inhibitors book, Amandeep Goyal; Austin S. Cusick; Blair Thielemier, 2020, Illustration of Renin-
Angiotensin Aldosterone system (RAAS) pathway. Contribute Austin Cusick and Amandeep Goyal, MD
Metabolism and Excretion

• Steroid hormones are metabolized in the liver where they

are reduced and conjugated with either glucuronic acid or
sulfate.
a) Approximately 20% to 30% of those metabolites are secreted
into the bile and then excreted in the feces.
b) The remainder are released into the blood to be excreted by
the kidney with urine.
These conjugate metabolites are soluble in blood or bile and don’t
need carrier proteins.
Action of
Cortisol
• Metabolic effect:
1. Carbohydrate metabolism:
a) Cortisol stimulates gluconeogenesis
in the liver by molblizing amino acids
from extra-hepatic tissues
(muscules) and by increasing the
enzymes of gluconeogenesis.
b) It decreases the utilization of glucose
by cells by decreasing glucose
transport into the cells.
c) It increases blood glucose levels and
this condition is called adrenal
diabetes.
Action of Cortisol

2. Protein Metabolism:
a) The principal effects of cortisol on the metabolic systems of
the body is reduction of protein stores in all body cells
except those of the liver. This is caused by both decresed
protein synthesis and increases catabolism of protein in the
cells.
b) It inhibits amino acid entery into all cells except the liver.
c) It increases amino acid concentration in blood.
d) It increases urea level in blood.
Action of Cortisol
3. Fat metabolism:
a) It mobilizes fatty acids from adipose tissues.
b) It increases free fatty acid concentration in blood.
c) It increases utilization of free fatty acids for energy.
d) It causes ketosis due to increased conversion of free fatty acids into
acetyl-CoA.
4. Electrolyte metabolism:
a) It promotes Na+ and Cl- retention from the renal tubules.
b) It increases excretion of K+ by kidneys.

5. Water metabolism:
It causes absorption of water from renal tubules.
Action of Cortisol
• Effect on host-defence mechanisms:
Suppress the immune response and inflammatory response by decreasing the
number of circulating leukocytes and the migration of tissue leukocytes.

• Other effects:
a) Necessary for maintenance of normal blood pressure and cardiac output.
b) It acts with the hormones of the adrenal medulla in allowing the organism to
respond to stress.
• In pathological and pharmacological quantities, glucocorticoids also have
other effects including:
1. Anti-inflammatory actions.
2. Suppression of immune responses.
3. Delayed wound healing.
Cortisol the stress hormone
Action of Mineralocorticoids

• The most active member of these hormones is the aldosterone.

• They act in the kidney to stimulate active sodium transport by the
distal convoluted tubules and collecting tubules, leading to Na+
retention.
• These hormones also promote the secretion of K+, H+ and NH4+ by
the kidney.
 Secreted by cells in the zona reticularis
Sex • The adrenal cortex secrets small
Hormones amounts of sex hormones:
1. Estrogens
2. Androgens
a) The primary and most
well-known androgen is
testosterone
b) The precursor of all
estrogens
Adrenocortical Diseases

• Overproduction of glucocorticoids (Cushing’s Syndrome)

1. Overproduction of ACTH
2. Hyperpigmentation: due to excess associated melanocyte stimulating
hormones
3. Metabolic manifestation due to excessive production of adrenal steroid
which includes:
a) Deficiency of potassioum and phosphorus.
b) Sodium retention which can lead to hypertension.
c) Oedema.
d) Glucose intolerance and diabetes mellitus.
e) Increased plasma fatty acids and redistribution of body fat, i.e.
truncal obesity.
 • Underproduction of glucocorticoids
Adrenocortica (Addison’s disease)
l Diseases 1. All three classses of adrenal
corticosteroids are decreased in
Addison’s disease.
 Glucocorticoids
 Mineralocorticoids
 Andregons
2. Common casuse is autoimmune
response to adrenal tissue.
3. It results in hypoglycemia,
anoroxia, weight loss,
intolerance to stress and severe
weakness.
 Adrenocortical
Diseases

Overproduction of
mineralocorticoids
(hyperaldosteronism)
• Primary hyperaldosteronism in:
Conn’s Syndrome
Adrenal hyperplasia
Congenital adrenal hyperplasia
• The classical manifestations include
hypertension, hypokalemia, hypernatremia
and alkalosis.
Hormones of Adrenal Medulla

• They include catecholamine hormones: epinephrine, norepinephrine (also called

Adrenaline and Noradrenaline) and dopamine.
• They are synthesized from tyrosine at storage sites: adrenergic neurons, sympathetic
ganglia, chromaffrin cells of adrenal medulla.
• In neurons: norepinephrine and dopamine are synthesized from tyrosine as follow:
1. Tyrosine is first hydroxylated to form 3,4-dihydrophenylalanine (dopa).
2. Dopa is decarboxyalted to dopamine, which is oxidized to norepinephrine by
dopamine B-oxidase.
• In adrenal medulla: synthesis of catecholamines is similar to synthesis in neuron;
however adrenal medullay cells contain phenylethanolamine N-methyltransferase. This
enzyme catalyzes the convervision of norepinephrine to epinephrine.
Functions of Catecholamines
• Norepinephrine and dopamine act as neurotransmitters in the brain and
at most sympathetic postganglionic endings.
Functions of Catecholamines

• Regulation of metabolism
Epinephrine and norepinephrine act as a regulators of metabolism:
a) Breakdown of glycogen (glycogenolysis) and lipids
(lipolysis).
b) Increase of output of the heart and blood pressure.
c) Relaxation of smooth muscles of bronchi and intestine.
The above reactions prepare the individual for emergencies and
are called ‘fright, fight or flight’ reactions.

Bioc 313