Cations inhibit specifically type I 5α-reductase found in human skin

Abstract

Steroid 5α-reductase catalyzes the reduction of testosterone into the very potent androgen dihydrotestosterone. Previously, we showed that human type I 5α-reductase is expressed mainly in the skin, whereas a type II 5α-reductase is more specifically expressed in the prostate. To assess the possible differential effects of various cations on the two types of 5α-reductase, we constructed expression vectors and transfected them into SW-13 cells, a human adrenal carcinoma cell line containing negligible endogenous 5α-reductase activity. The expressed 5α-reductases were analyzed for their sensitivity to Li, Ca, Cd, Gu, Mg, Mn, Ni, Zn, and Fe. The results showed that type I 5α-reductase was strongly inhibited by Cd, Gu, and Zn and moderately inhibited by Ni and Fe, with 50% inhibitory concentration values of 0.9, 1.9, 2.0, 169.2, and 174.3 μM, respectively. In contrast, type II 5α-reductase activity was inhibited only by Gu, with a 50% inhibitory concentration value of 19.2 μM. The data showed that cations could specifically control 5α-reductase activity expression, which is more strongly inhibited in a target tissue, especially the skin.