Cations Inhibit Specifically Type I 5α-Reductase Found in Human Skin

Abstract

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