Steroidogenesis by zone

Outline of the organization of the major enzymatic steps in steroid biosynthesis in the adrenal cortex, with emphasis on the pathways to androgens.

The top (dotted blue) row shows the zona glomerulosa pathway to aldosterone that is angiotensin responsive. The middle (diagonally lined orange) row shows the pathway to cortisol that occurs in the zona fasciculata, and the lower (solid green) row shows the pathways to DHEAS and other androgenic 17-ketosteroids (all C19 steroids) that occur in the zona reticularis; these zones are ACTH responsive. The dashed box surrounds pathways that are common to all adrenocortical zones and theca and Leydig cells of the gonads. The steroidogenic enzymes are in bold italics, and cofactors are in plain italics.
Cytochrome P450 enzyme activities are: P450scc (20,22 side-chain cleavage), P450c17 (17-alpha-hydroxylase and 17,20-lyase), P450c21 (21-hydroxylase), P450c11β2 (11-beta-hydroxylase type 2, aldosterone synthase), P450c11β1 (11-beta-hydroxylase type 1), and P450aro (aromatase).
Non-P450 enzyme activities are carried out by StAR (steroidogenic acute regulatory protein), 3βHSD2 (delta-5-isomerase/3-beta-hydroxysteroid dehydrogenase type 2), 17βHSD5 (17-beta-hydroxysteroid dehydrogenase type 5), and SULT2A1 (sulfotransferase type 2, family A1).
The steroids to the left of 3ßHSD2 have the delta-5-3-beta-hydroxysteroid configuration, while those to the right have the delta-4-3-ketosteroid configuration.
Cofactors clinically relevant to androgen biosynthesis are POR (P450 oxidoreductase), CYb5 (cytochrome b5), and PAPSS2 (3'phosphoadenosine-5'phosphosulfate synthase type 2).
Since the mineralocorticoid pathway is not the primary point of the figure, it is oversimplified between DOC and aldosterone, not showing corticosterone and 18-hydroxycorticosterone, the successive 11β- and 18-hydroxyl intermediates that are formed from DOC by P450c11ß2 in the process of synthesizing aldosterone. P450c11β1 is not expressed in the zona glomerulosa but is prominently expressed in the zona fasciculata, where it forms corticosterone from DOC.

DOC: deoxycorticosterone; Cmpd S: compound S (11-deoxycortisol); DHEAS: dehydroepiandrosterone sulfate; ACTH: adrenocorticotropic hormone.

Modified with permission from: Rosenfield RL. Clinical review: Identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92:787. http://jcem.endojournals.org/. Copyright © 2007 The Endocrine Society.

Enzyme abbreviations according to Miller WL, Auchus RJ. The molecular biology, biochemistry and physiology of human steroidogenesis and its disorders. Endocrine reviews 2011; 32:81-151.

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Steroidogenesis by zone