New Hormonal Therapies for Castration Resistant Prostate Cancer

In the classical pathway (solid gray arrow), C21 precursors (pregnenolone and progesterone) are converted to the C19 adrenal androgens DHEA and androstenedione (AED) by the sequential hydroxylase and lyase activity 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 backdoor pathway to DHT synthesis (short gray arrows), C21 precursors are first acted upon by SRD5A and the reductive 3α-HSD activity of the AKR1C family member, AKR1C2, followed by conversion to C19 androgens via the lyase activity of CYP17A. DHT is subsequently generated by the action of HSD17B3 and an oxidative 3α-HSD enzyme, including HSD17B6 (also called RL-HSD) or HSD17B10 (as well as RODH4, RODH5 and NT 3α-HSD, not shown). Adapted from Mostaghel EA, Nelson PS. Intracrine androgen metabolism in prostate cancer progression: mechanisms of castration resistance and therapeutic implications. Best Pract Res Clin Endocrinol Metab. 2008;22:243, with permission.

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New Hormonal Therapies for Castration Resistant Prostate Cancer. () Elahe A. Mostaghel, et al. Endocrinol Metab Clin North Am. ;40(3):625-642. Figure: F1. All organisms Homo sapiens Danio rerio

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