ADRENAL GLAND-PHYSIOLOGY

DR G S RANDHAWA

• Adrenal cortex and the adrenal medulla are best considered as two separate organs,theformer endocrine and the latter neurocrine.

• Three main zones of adrenal cortex are –

• Zona glomerulosa-mineralocorticoids

• Zona fasciculata-glucocorticoids

• Zona reticularis-androgens

-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.

• 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.

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.

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.

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.

Zona glomerulosa

• Outermost

• Only zone contains enzyme aldosteronesynthase(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.

Glomerulosa...cond..

• Aldosterone secretion controlled by angiotensionll 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.

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.

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.

Zona reticularis

• Innermost layer

• Enzymes include-17-alfa-hydroxylase and 17,20-lyase

• Lead to production of DHEA-dehydroepiandrosterone and sulfatedDHEA(DHEA-S); and androstenedione

• Under control of ACTH

• Exhibits circadian pattern

Reticularis...cond...

• Maximally produced steroid hormone(>20mg/day) but least important for pysiological homeostasis.

• Pharmacological manipulation gives good results in cases of cancer prostate.

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%)

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.

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.

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.