CHARACTERIZATION, EXPRESSION, AND IMMUNOHISTOCHEMICAL LOCALIZATION OF5-ALPHA-REDUCTASE IN HUMAN SKIN

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