Inhibition of steroid 5α-reductase from human skin fibroblasts by 17β-N, N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one

The capacity of 17β-N, N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one (DMAA) to inhibit competitively steroid 5α-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 5α-reduction of testosterone, 4-androstene-3,17-dione, 20α-hydroxy-4-pregnen-3-one and cortisol, and appears to be weakly bound to serum protein. The inhibitor is particularly effective (apparent K_i 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 5α-reduction of steroid hormones in intact animals and in embryos.