Pathways of androgen biosynthesis

The pathways of androgen biosynthesis. 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. DHEA and AED are converted to testosterone by a series of reactions involving the activity of HSD3B1 and 2, HSD17B3 and AKR1C3 enzymes. Testosterone is converted to the potent androgen DHT by the activity of SRD5A1 and 2. Oxida-tive 3 α-HSD enzymes (including HSD17B6 (RL-HSD), HSD17B10, HSD17B13 (DHRS9), RODH4 and RDH5) can act to inhibit the pre-receptor catabolism of DHT. An alternative pathway (short gray arrows) has also been proposed in which C21 precursors are first acted upon by SRD5A and the reductive activity of AKR1C2, followed by CYP17A1, HSD17B3 and subsequent oxidation to DHT 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 Me-tab. 2008;22:243, with permission (pending).

Publication

Resistance to CYP17A1 inhibition with abiraterone in castration resistant prostate cancer: Induction of steroidogenesis and androgen receptor splice variants. () Elahe A. Mostaghel, et al. Clin Cancer Res. ;17(18):5913-5925. Figure: F6. All organisms Homo sapiens Danio rerio

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