S1  STEROIDOGENIC ENZYMES: BIOCHEMICAL CHARACTERISTICS, TISSUE DISTRIBUTION AND MUTATIONS

Andersson S.  Dept. of Obstetrics-Gynecology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Androgens play a pivotal role in the growth of pubic and axillary hair. Paradoxally, androgens stimulate growth of beard hair, whereas in the scalp, androgens inhibit hair growth, particularly in persons with genetic predisposition to androgenic alopecia.

The major androgen testosterone is principally formed in the testes of males and the ovaries of females. The synthesis of testosterone in the gonads involve the four enzymes cytochrome P-450 side-chain cleavage enzyme, cytochrome P-450 17a-hydroxylase/lyase, 3b-hydroxysteroid dehydrogenase, and 17b-hydroxysteroid dehydrogenase. A significant part of the plasma-borne testosterone will be converted in androgen target tissues, such as the skin, to the more potent androgen dihydrotestosterone by the steroid 5a-reductase type 1 and type 2 isoenzymes. Dihydrotestosterone, which binds to the nuclear androgen receptor with much greater affinity than testosterone, is believed to be the androgen responsible for the process leading to androgenetic alopecia. This notion stems from the observation that men with steroid 5a-reductase2 deficiency do not develop male pattern baldness. Consequently, the 5a-reductase type 2 isoenzyme-specific inhibitor finasteride (Merck Sharp & Dohme) has proven efficacious in promoting hair growth as a consequence of lowering scalp and plasma dihydrotestosterone levels. By immunohistochemical analysis of human scalp, it has been shown that the type 2 isoenzyme is predominantly expressed in the root sheath of the hair follicle, in contrast to 5a-reductase type 1, which is expressed to high levels in the sebaceous glands. Thus the function of the type 1 isoenzyme may be to locally convert circulating testosterone to dihydrotestosterone for sebum production.