title: Cations inhibit specifically type I 5 alpha-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.
authors.affiliation: Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: I
authors.initials: I
authors.lastname: López-Solache
authors.forename: F
authors.initials: F
authors.lastname: Labrie
authors.forename: V
authors.initials: V
authors.lastname: Luu-The
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000838:Anions / Q000494:pharmacology; D001483:Base Sequence; D002104:Cadmium / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000494:pharmacology; D008969:Molecular Sequence Data; D009532:Nickel / Q000494:pharmacology; D012867:Skin / Q000201:enzymology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
chemical_list: D058891:5-alpha Reductase Inhibitors; D000838:Anions; D002412:Cations; D002104:Cadmium; D003300:Copper; D009532:Nickel; D007501:Iron; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D015032:Zinc