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.
Takahashi
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MRC Group in Molecular Endocrinology, CHUL Research Centre, Quebec, Canada.
Luu-The
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Labrie
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D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D001378:Azasteroids / Q000494:pharmacology*; D002848:Chromatography, DEAE-Cellulose; D003489:Cyanoketone / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D045167:Progesterone Congeners / Q000494:pharmacology*; D011375:Progesterone Reductase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D013251:Steroid Isomerases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification
C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D001378:Azasteroids; D009097:Multienzyme Complexes; D045167:Progesterone Congeners; D013196:Dihydrotestosterone; D003489:Cyanoketone; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D015096:3-Hydroxysteroid Dehydrogenases; D011375:Progesterone Reductase; D013251:Steroid Isomerases