Adrenal gland physiology

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.

14. 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%)

15. 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.

16. 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 .

17. 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.