Reduction of dihydrotestosterone to androstanediols by human female skin in-vitro

Abstract

The in vitro metabolism of [ 3H]-17β-hydroxy-5α-androstan-3-one (DHT) was studied in subcellular fractions of pubic skin. The metabolites obtained were mainly: 5α-androstan-3α,17β-diol (3α-diol) and 5α-androstan-3β,17β-diol (3β-diol) produced in both the soluble fraction (cytosol) and microsomal fraction. These two enzymatic reactions were NADH and/or NADPH dependent. The formation of both diols was studied as a function of protein concentration, pH and temperature. In cytosol incubations supplemented with NADPH, the rate of formation of 3α-diol from DHT was greater than that of 3β-diol, whereas in NADH supplemented cytosol, 3β-diol was the major metabolite of DHT. The apparent K M obtained were 9 μM for 3α-diol and 14.2 μM for 3β-diol in the presence of optimal NADPH concentration, 20μM for 3α-diol and 3.8μM for 3β-diol in the presence of optimal NADH concentration. In incubations with microsomes, 3β-diol was the main metabolite whatever the cofactor used. The reversibility of the reaction was zero for 3β-ketoreductase and very low (1.4–3.5%) for 3α-ketoreductase in contrast to what is observed in prostate. The differences obtained in cofactor dependency for 3α 3β diol formation in human skin microsomes and cytosol is of interest in the understanding of active androgen metabolism in human skin.