Characterization, Expression, and Immunohistochemical Localization of 5α-Reductase in Human Skin

Human skin has been shown to contain a high level of 5α-reductase activity, the enzyme that catalyses the conversion of the weak androgen testosterone into dihydrotestosterone, the most potent androgen. Because two types of 5α-reductase genes have been characterized in humans, we have cloned 5α-reductase cDNAs from adult human keratinocyte and skin fibroblast cDNA libraries to identify and gain better knowledge of the 5α-reductase expressed in normal human skin. Nucleotide sequence analysis shows that the clones obtained correspond to the type I 5α-reductase. RNase protection analysis using (poly A)⁺ RNA obtained from human skin and prostate also confirms that type I 5α-reductase is the predominant type expressed in normal skin, whereas type II 5α-reductase is the major form found in the prostate. Following polymerase chain reaction amplification of human keratinocyte and skin fibroblast cDNA, a low level of type II 5α-reductase cDNA has been detected. Using antipeptide antibodies raised in rabbits against the peptide sequence covering amino acids 227 – 240 to perform immunohistochemical localization of 5α-reductase, we have found that 5α-reductase is distributed in sweat and sebaceous glands, as well as in the epidermal cell layers, thus providing the basis for the important role of androgens in human skin and its appendages.