Role of AKR1C3 in androgen biosynthesis in human prostate. The conversion of C21 steroids pregnenolone and progesterone to the corresponding C19 steroids dehydroepiandrosterone (DHEA) and 4-androstene-3,17-dione is catalyzed by CYP17 (P45017A1); and the preferred route is from pregnenolone. The evidence for intratumoral biosynthesis of C19 steroids from C21 steroids is scant and the reactions occur predominately in the adrenal. The conversion of progesterone to desoxycorticosterone is adrenal specific and is a side effect of abiraterone acetate treatment leading to mineralocorticoid excess. HSD3B1, 3β-hydroxysteroid dehydrogenase type 1, SRD5A, steroid 5α-reductase type 1 and type 2. Reproduced with permission from Adeniji AO, Twenter BM, Byrns MC, Jin, Y, et al. Development of potent and selective inhibitors of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase) based on N-phenyl-aminobenzoates and their structure-activity relationships. J Med Chem 2012;55:2311–23 Copyright American Chemical Society.