Synthesis of adrenal steroids

Adrenal cortical hormones are steroids having the base structure of cyclopentano perhydrophenanthrine ring. All steroid hormones are synthesized from cholesterol. The cholesterol for steroid synthesis is mainly derived from circulating blood and is stored within steroid synthesizing cells in large quantities as lipid droplets or ester form.

A very small amount of cholesterol is synthesized by cortical cells. There are three types of steroids-

1. C21 steroids have 2 carbon side-chain at position 17
2. C19 steroids have keto or hydroxyl group at C17 and called as 17-ketosteroids
3. C18 steroids have keto or hydroxyl group at C17, no CH3 group at C10

Adrenal steroids are mostly C21 and C19 steroids. C19 steroids have androgenic activity and C21 are either mineralo or glucocorticoids.

The initial step in steroid formation is the hydrolysis of cholesterol ester by the enzymatic cleavage of carbon side chain from the steroid molecules, leaving a C‑21 steroid, the pregnenolone.

ACTH promotes adrenocortical steroidogenesis through the activation of cholesterol desmolase and is important in the conversion of cholesterol to pregnenolone and in C‑17 hydroxylation. This step occurs within the mitochondria. This is followed by hydroxylation at C‑21 by C‑21 hydroxylase.

The difference between the mineralocorti­coids (aldosterone) and glucocorticoids (cortisol) is that only the glucocorticoids have a hydroxyl group on C‑17, the hy­droxylation is done by 17 α -hydroxylase, the enzyme present only in the cells of zona fasciculata but absent in zona glomerulosa.

Both aldosterone and glucocorticoids have hydroxyl group at C‑11. O₂ at C18 position is important for mineralocorticoid activity.

In zona glomerulosa, 11 hydroxylase and 17 hydroxylase are absent. Deoxycorticosterone is converted to aldosterone through corticosterone by the enzyme aldosterone synthase present only in zona glomerulosa.

Birds, mice and rats secrete mostly corticosterone, dogs secrete equal amounts of cortisol and corticosterone, cat, sheep, monkeys and human secrete predominantly cortisol.

75% of glucocorticoid is carried in plasma in association with specific binding globulins, corticosteroid binding globulin (CBG) called transcortin, 20% in albumin and 5% in free form. 50% aldosterone is carried in albumin, 10% with CBG and the rest in free-state.

Plasma half life of cortisol is about 60 to 90 min and aldosterone is 20 min.