adrenal gland, physiology, brief anatomy, functions

1. ADRENAL GLAND-PHYSIOLOGY
DR G S RANDHAWA

2. • Adrenal cortex and the adrenal medulla are
best considered as two separate organs,the
former endocrine and the latter neurocrine.
• Three main zones of adrenal cortex are –
• Zona glomerulosa-mineralocorticoids
• Zona fasciculata-glucocorticoids
• Zona reticularis-androgens

3. -continued.......
• Ratios and types of enzymes in each zone of the
cortex vary, resulting in different hormonal
products for each region.
• Aldosterone levels are primarily controlled by
angiotensin ll through renin-angiotensin-
aldosterone system and directly by serum
potassium levels.ACTH is less important in
controlling this region’s functions that is why
glomerulosa does not get atrophied in cases with
total pituitary failure.

4. • Cortisol is the primary glucocorticoid in
humans,and its secretion is under tight control of
ACTH.
• Pharmacological manipulation of adrenal
androgen production is an increasingly targeted
strategy for treatment of advanced cancer of
prostate.
• Epinephrine, norepinephrine and dopamine
collectively known as catecholamines, are
produced from amino acid tyrosine and
modulaters of systemic stress response.

5. Adrenal cortex
• Multistep synthetic pathway
• Numerous enzymes – specific to particular zone
• Common precursor is cholesterol derived from
low- density triglycerides(LDL)
• Steroid hormone receptors absent on cell
membrane of target tissues instead diffuse
passively into cells and binds with receptors
present intracellularily
• This hormone receptor complex in turn binds
with target DNA to modulate gene transcription.

6. Contd.....
• Zona glomerulosa-mineralocorticoids-100-150
mcg/day.
• Zona fasciculata-glucocorticoids-10-20 mg/day.
• Zona reticularis-androgens->20mg/day.
• Primary effects of mineralocorticoids-
Action-renal reabsorption of sodium
Effect-increase blood volume,increase blood
pressure; decrease urine sodium. Site of action is
distal tubule connecting collecting duct.

7. Contd....
• Renal chloride reabsorption,increase serum
chloride; site of action distal tubule
connecting collecting duct segment
• Renal potassium secretion, decrease in serum
potassium;distal tubule connecting segment
collecting duct
• Renal proton secretion,increases urine NH; as
result of Na reabsorption.

8. Zona glomerulosa
• Outermost
• Only zone contains enzyme aldosterone
synthase(CYP11B2)
• Aldosterone regulates electrolyte metabolism by
stimulating distal nephron cells to reabsorb Na
and Cl and secreting H and K
• Profound effect on total body Na but conc.
Remains same due to water absorption along
with sodium.total body volume of Na is
increased.

9. Glomerulosa...cond..
• Aldosterone secretion controlled by angiotension
ll through renin-angiotensin-aldosterone system.
ACTH have very little role to play.
• This zone does not atrophy even after total
pituitary failure.
• Atrial natriuretic peptide is the main inhibitory
regulator of aldosterone secretion providing
important link between cardiac,adrenal and renal
funtion.

10. Zona fasciculata
• Produces glucocorticoids
• Cortisol is the primary glucocorticoid in
humans
• Enzymes-17-alfa-hydroxylase,21-hydroxylase
and11-beta-hydroxylase present in this zone
lead to production of cortisol under the tight
control of ACTH secreted by anterior pituitary.
• Classic feedback mechanism involves
hypothalamus-pituitary-adrenal axis.

11. Fasciculata ...cond..
• Cortisol secretion follows strict circadian
scedule maximum secretion during early
morning hours
• Essential for life-modulate complex
physiological pathways including—
• Metabolism,immunity,maintenence of
intravascular volume,regulation of blood
pressure and complex modulation of CNS with
effects on mood,sleep and memory.

12. Zona reticularis
• Innermost layer
• Enzymes include-17-alfa-hydroxylase and
17,20-lyase
• Lead to production of DHEA-
dehydroepiandrosterone and sulfated
DHEA(DHEA-S); and androstenedione
• Under control of ACTH
• Exhibits circadian pattern

13. Reticularis...cond...
• Maximally produced steroid
hormone(>20mg/day) but least important for
pysiological homeostasis.
• Pharmacological manipulation gives good
results in cases of cancer prostate.

15. ADRENAL MEDULLA-physiology
• Less than 10% of total adrenal mass.
• Neither function nor embrologically related to
cortex.
• Part of ANS
• Chromaffin cells exhibit characteristics of
sympathetic ganglionic cells
• Secretes epinephrine(80%),
norepinephrine(19%) and dopamine(1%)

16. Adrenal medulla...cont’’
• Collectively called catecholemines
• Produced from amino acid tyrosine and
modulate systemic stress response.
• Effect mediated through their bindind to
adenorecepters located on target organs.
• PNMT enzyme phenylethanolamine-N-methyl
transferase converts norepinephrine to
epinephrine is present almost exclusively in
medullary cells.

17. Adrenal medulla...cond..
• Function of PNMT is enhanced by cortisol the
only link between cortex and medulla.
• Stored in intracellular vesicles. Released in blood
through exocytosis.
• Metabolise into three products viz.
Metanephrine, normetanephrine and
vanillylmandelic acid(VMA).
• Two enzymes catechol-o-methyltransferase
(COMT) and monoamine oxidase(MAO) are
responsible for metabolism of catecholemines.

18. Adrenal medulla...cond...
• Over 90% of metanephrine and >20% of
normetanephrine in blood stream are derived
from adrenal medulla.
• Can be measured and useful in diagnosis of
pheochromocytomas.
• Excreted in sulfonated form mostly as VMA in
urine.can be measured.