Inhibitory effect of synthetic progestins, 4-MA and cyanoketone on human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene-isomerase activity.
Human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene isomerase (3 beta-HSD) purified from human placenta transforms C-21 (pregnenolone and 17 alpha-hydroxy pregnenolone) as well as C-19 (dehydroepiandrosterone and androst-5-ene-3 beta, 17 beta-diol) steroids into the corresponding 3-keto-4-ene-steroids and is thus involved in the biosynthesis of all classes of hormonal steroids. Trilostane, epostane and cyanoketone are potent inhibitors of 3 beta-HSD with Ki values of approximately 50 nM. 4-MA, a well known 5 alpha-reductase inhibitor, is also a potent inhibitor of 3 beta-HSD with a Ki value of 56 nM. Synthetic progestin compounds such as promegestone and RU2323 show relatively strong inhibitory effects with Ki values of 110 and 190 nM, respectively. Cyproterone acetate, a progestin used in the treatment of hirsutism, acne and prostate cancer as well as norgestrel and norethindrone that are widely used as oral contraceptives also inhibit 3 beta-HSD activity at Ki values of 1.5, 1.7 and 2.5 microM, respectively.
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4-MA progestin promegestone RU2323 Cyproterone acetate progestin norgestrel norethindrone progestins 4-MA pregnenolone cyanoketone 3 beta-hydroxysteroid Human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene isomerase 3 beta-HSD 5 alpha-reductase 3 beta-HSD 3 beta-HSD 3 beta-HSD human placental 3 beta-hydroxysteroid dehydrogenase/5----4-ene-isomerase 17 alpha-hydroxy pregnenolone 3 beta-hydroxysteroid dehydroepiandrosterone androst-5-ene-3 beta, 17 beta-diol 3-keto-4-ene-steroids Trilostane epostane cyanoketone