The document summarizes the adrenal glands, which consist of an outer cortex and inner medulla. The cortex produces steroid hormones like cortisol and aldosterone. Cortisol regulates metabolism and aldosterone regulates sodium levels. The medulla produces catecholamines like epinephrine and norepinephrine which prepare the body for stress by increasing heart rate and blood flow. Cholesterol is the precursor for steroid hormone synthesis, while tyrosine is the precursor for catecholamines. The hormones are regulated by ACTH and have important metabolic effects on carbohydrate, lipid, and physiological functions.

1. ADRENALS - CHEMISTRY AND
BIOSYNTHESIS OF ADRENAL
MEDULLARY AND ADRENAL CORTICAL
HORMONES
Dr. ACHLA JAIN
GUEST LECTURER
SOS IN LIFE SCIENCES
PT. RAVISHANKAR SHUKLA UNIVERSITY,
RAIPUR

2. ADRENAL GLANDS
The adrenals are orange-colored glands that sit on top of
the kidneys near the spine, just underneath the last rib
and extending down about an inch.

3. The glands consist of two layers;
the cortex and medulla.
The adrenal cortex is composed of three zones.
From the outer to inner, the layers are;
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis

4. All these zones produce hormones derived from
cholesterol, which is abundant in the cells.
The adrenal cortex represents 80-90% of the
adrenal gland.
1. Zone of glomerulosa
Aldosterone is secreted from this zone which is
the major hormone controlling the sodium and
potassium levels, and thus fluid balance, within
bloodstream, cells and interstitial fluids. It is also
called mineralocorticoids.

5. 2. Zone of fasciculata
Coritsol (hydrocortisone) is produced, affects glucose,
amino acid and fat metabolism, which is called
glucocorticoids. Cells of this zone are arranged into
fascicles separated by venous sinuses.
3. Zone of reticularis
Dehydroepiandrosterone (DHEA)-precursor for
androgen is synthesized.

7. 1. SYNTHESIS OF STEROID HORMONES
i. Cholesterol is first acted upon by desmolase and a 6-carbon
unit is cleaved off, forming the 21 carbon steroid,
pregnenolone. It is a common precursor for all the steroid
hormones. ACTH stimulates this step. This is the rate limiting
step for synthesis of all steroid hormones.
ii. Progesterone is the first steroid hormone
formed from pregnenolone in two steps. The beta hydroxyl
group is converted to a keto group by a 3-beta-ol-
dehydrogenase and the Δ5 double bond shifted to Δ4.
iii. Progesterone is further converted into glucocorticoids,
mineralocorticoids and sex steroids .

11. iv. The major adrenal glucocorticoids are cortisol,
cortisone and corticosterone in that order. The
major mineralocorticoid is aldosterone, but 11- deoxy-
corticosterone and corticosterone also have significant
mineralocorticoid activity.
v. These reactions are effected by hydroxylation.
These specific hydroxylases are monooxygenases.
All these enzymes are NADPH dependent.
vi. ACTH stimulates the synthesis of all steroid
hormones by activating desmolase so that the
availability of pregnenolone is increased.

13. 2. SECRETION OF ADRENAL HORMONES
i. Secretion of all adrenocortical hormones is under the control
of ACTH.
ii. The diurnal variation of secretion of cortisol (highest
values early in the morning and minimum at night) parallels
the pulsatile release of ACTH from anterior pituitary under
the influence of CRF.
iii. Cortisol exerts the negative feedback effect on ACTH
secretion.
iv. ACTH increases the secretion of aldosterone.
v. The level of aldosterone is affected by position, highest
values in upright posture and lowest while lying down.
vi. All steroid hormones act through intracellular
messengers and increase the rate of transcription.

14. 3. TRANSPORT AND METABOLISM
i. Approximately 70% of cortisol in blood is bound to an
alpha-1-globulin called cortisol binding globulin
(CBG) or transcortin.
ii. About 20% is bound to albumin and the rest is free,
which is the biologically active fraction. The half-life of
cortisol is about 2 hours.
iii.The steroid hormones are metabolized and inactivated
by the liver. The major processes are reduction and
conjugation.
iv. The C21 steroids are reduced to their tetrahydro
derivatives, which are excreted as their glucuronides or
sulfates in urine.

15. THE ADRENAL MEDULLA
The functional unit of the adrenal medulla is the chromaffin
cell, which functions as a neuroendocrine cell. In response
to stimulation, chromaffin cells secrete the hormones
epinephrine (adrenaline) and norepinephrine
(noradrenalin) directly into the blood.
The medulla is involved in extreme stress, epinephrine
and norepinephrine both work with cortisol from the adrenal
cortex. Epinephrine and norepinephrine are important
mainly in crisis situations. The adrenal medulla is primarily
involved in the production of catecholamines; epinephrine
and norepinephrine.

16. In fetal life, the adrenal medulla plays a role in
the autonomic nervous system. The medulla acts
as a sympathetic ganglion with the
postganglionic cells lacking axons. Through
sympathetic preganglionic fiber stimulation, the
medullary cells secrete catecholamines. The
adrenal medulla represents only 10-20% of the
adrenal gland.

17.  noradrenaline 20% 1.2 - 3.4 nmol/l
- 5 - 6 fold increase exerts biological action
 adrenaline 80% 0.1 - 0.8 nmol/l
2 fold increase can elicit physiological response
- These hormones prepare the body to deal with short- term
stress.

18. CATECHOLAMINES BIOSYNTHESIS
1. Tyrosine is precursor for the synthesis of
catecholamines.
2. The catecholamine are produced in response to
fight, fright and flight (3F). These include
emergencies like shock, cold, fatigue, emotional
condition like anger.

20. BIOCHEMICAL FUNCTION OF CATECHOLAMINE
1. Effect on carbohydrate metabolism: Both of them can
increase glycogenolysis and gluconeogenesis and decrease
glycogenesis.
 Catecholamine promote the release of glucose from liver and
 Decrease its utilization by muscle; Epinepherine inhibits
insulin secretion but promote glucagon secretion.
2. Effect on lipid metabolism: Both of them enhance the
breakdown of TAG in adipose tissue. This cause increase in
the free fatty acid in the circulation which are effectively
utilized by the heart and muscle as fuel source.
3. Effect on physiological function: Catecholamines
increase cardiac output, blood pressure and oxygen
consumption. They cause smooth muscle relaxation in
bronchi, GIT and blood vessels supplying skeletal muscle.