Classical and back-door pathways of androgen biosynthesis

The classical and back-door pathways of androgen biosynthesis. In the classical pathway (solid gray arrow), C21 precursors (pregnenolone and progesterone) are converted to the C19 adrenal androgens dihydroepiandrosterone (DHEA) and androstenedione (AED) by the sequential hydroxylase and lyase activities of CYP17A1. Circulating adrenal androgens (including the sulfated form of DHEA, DHEA-S), enter the prostate and can be converted to testosterone by a series of reactions involving the activity of HSD3B, HSD17B and AKR1C enzymes. Testosterone is then converted to the potent androgen DHT by the activity of SRD5A. In the back-door pathway to DHT synthesis (short gray arrows), C21 precursors are first acted upon by SRD5A and the reductive 3α-hydroxysteroid dehydrogenase (3α-HSD) activity of AKR1C family members, followed by conversion to C19 androgens via the lyase activity of CYP17A, and subsequently to dihydrotestosterone (DHT) by the action of HSD17B3 and an oxidative 3α-HSD enzyme.

Publication

Intracrine androgen metabolism in prostate cancer progression: mechanisms of castration resistance and therapeutic implications. () Elahe A. Mostaghel, et al. Best Pract Res Clin Endocrinol Metab. ;22(2):243-258. Figure: F1. Homo sapiens

Disease mentions