pregnenolone
Summary
Pregnenolone is the first steroid formed from cholesterol by cholesterol desmolase and is the common precursor of every steroid hormone. From pregnenolone the pathway branches to mineralocorticoids, glucocorticoids, androgens, and oestrogens.
Detail
Pregnenolone is converted either by 3-beta-hydroxysteroid dehydrogenase to progesterone, feeding the mineralocorticoid and glucocorticoid arms, or by 17-alpha-hydroxylase to 17-hydroxypregnenolone and onward to DHEA and the sex steroids. Its position at the head of the pathway explains the pattern of the congenital adrenal hyperplasias: a block distal to pregnenolone shunts substrate into whichever branches remain open. In 21-hydroxylase deficiency, the commonest form, cortisol and aldosterone fall while androgens rise, producing salt wasting with virilization; in 17-alpha-hydroxylase deficiency, androgens and cortisol fall while mineralocorticoids rise, producing hypertension with hypokalaemia and absent secondary sexual characteristics; in 11-beta-hydroxylase deficiency, 11-deoxycorticosterone accumulates and causes hypertension with virilization. Pregnenolone itself has no significant hormonal activity.
Sources
- First Aid for the USMLE Step 1
- Lippincott Illustrated Reviews: Biochemistry
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