Chen W, Zouboulis C C, Orfanos C E
Department of Dermatology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany.
Dermatology. 1996;193(3):177-84. doi: 10.1159/000246242.
5 alpha-Reductase, the enzyme system that metabolizes testosterone into dihydrotestosterone, occurs in two isoforms. The type 1 isozyme is composed of 259 amino acids, has an optimal pH of 6-9 and represents the 'cutaneous type'; it is located mainly in sebocytes but also in epidermal and follicular keratinocytes, dermal papilla cells and sweat glands as well as in fibroblasts from genital and non-genital skin. The type 2 isozyme is composed of 254 amino acids, has an optimal pH of about 5.5 and is located mainly in the epididymis, seminal vesicles, prostate and fetal genital skin as well as in the inner root sheath of the hair follicle and in fibroblasts from normal adult genital skin. The genes encoding type 1 and type 2 isozymes are found in chromosomes 5p and 2p, respectively, and each consists of 5 exons and 4 introns. During the last decade, several steroid analogues and non-steroid agents have been developed to interfere with 5 alpha-reductase activity. Finasteride, which has a higher affinity for the type 2 isozyme, is the first 5 alpha-reductase antagonist clinically introduced for treatment of benign prostate hyperplasia. The clinical evaluation of finasteride or other 5 alpha-reductase inhibitors in the field of dermatology has been very limited; in particular, those that selectively bind to type 1 isozyme (e.g. MK-386, LY191704) may be regarded as candidates for treatment of androgen-dependent skin disorders such as seborrhoea, acne, hirsutism and/or androgenetic alopecia.
5α-还原酶是一种将睾酮代谢为二氢睾酮的酶系统，它有两种同工型。1型同工酶由259个氨基酸组成，最适pH值为6 - 9，代表“皮肤型”；它主要位于皮脂腺细胞中，但也存在于表皮和毛囊角质形成细胞、真皮乳头细胞和汗腺以及生殖器和非生殖器皮肤的成纤维细胞中。2型同工酶由254个氨基酸组成，最适pH值约为5.5，主要位于附睾、精囊、前列腺和胎儿生殖器皮肤以及毛囊内根鞘和正常成年生殖器皮肤的成纤维细胞中。编码1型和2型同工酶的基因分别位于5号染色体短臂和2号染色体短臂上，每个基因都由5个外显子和4个内含子组成。在过去十年中，已经开发出几种类固醇类似物和非类固醇药物来干扰5α-还原酶的活性。非那雄胺对2型同工酶具有更高的亲和力，是临床上首个用于治疗良性前列腺增生的5α-还原酶拮抗剂。非那雄胺或其他5α-还原酶抑制剂在皮肤病学领域的临床评估非常有限；特别是那些选择性结合1型同工酶的药物（如MK - 386、LY191704）可被视为治疗雄激素依赖性皮肤病如脂溢性皮炎、痤疮、多毛症和/或雄激素性脱发的候选药物。
