Inhibition of steroid 5 alpha-reductase from human skin fibroblasts by 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one.
The capacity of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (DMAA) to inhibit competitively steroid 5 alpha-reductase has been confirmed in human foreskin fibroblasts. The inhibitor works equally well in homogenates and in intact cells, is rapidly reversible, does not influence the amount of the enzyme, is equally effective in inhibiting the 5 alpha-reduction of testosterone, 4-androstene-3,17-dione, 20 alpha-hydroxy-4-pregnen-3-one and cortisol, and appears to be weakly bound to serum protein. The inhibitor is particularly effective (apparent Ki of approximately 3 nM) at the optimal pH of the enzyme (pH 5.5) and has no effect in the alkaline range (pH 9.0). DMAA appears to be a steroid that will be useful in the investigation of 5 alpha-reduction of steroid hormones in intact animals and in embryos.
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000735:Androstenedione / Q000378:metabolism; D001378:Azasteroids / Q000494:pharmacology*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007700:Kinetics; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D012867:Skin / Q000201:enzymology*; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; D004092:20-alpha-Dihydroprogesterone; D013739:Testosterone; D000735:Androstenedione; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D010088:Oxidoreductases; D015067:17-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone