The 5 alpha-reductase system and its inhibitors. Recent development and its perspective in treating androgen-dependent skin disorders.

Abstract

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.