Steroidogenic enzymes in skin

The gonadal synthesis of testosterone from cholesterol involves four enzyme s, namely, cytochrome P-450 side-chain cleavage enzyme, cytochrome P-450 17 alpha -hydroxylasellyase, 3 beta -hydroxysteroid dehydrogenase, and 17 bet a -hydroxysteroid dehydrogenase. A significant part of the plasma--borne te stosterone is converted in androgen target tissues, such as the skin, to th e more potent androgen dihydrotestosterone by the steroid 5 alpha -reductas e type 1 and type 2 isoenzymes. Dihydrotestosterone, which binds to the nuc lear androgen receptor with much greater affinity than testosterone, is the androgen responsible for a process leading to androgenetic alopecia. Conse quently, the 5 alpha -reductase inhibitor finasteride was developed and has proven efficacious in promoting hair growth as a consequence of lowering s calp and plasma dihydrotestosterone levels. In contrast to the direct synth esis of dihydrotestosterone from testosterone, biologically inactive C-19-s teroids produced by glandular and peripheral tissues may also feed into the scalp skin production of dihydrotestosterone by the local expression of re ductive 17 beta -hydroxysteroid dehydrogenase, oxidative 3 alpha -hydroxyst eroid and 3 beta -hydroxysteroid dehydrogenase enzymes. Aberrant expression of one or more of these enzymes, could conceivably result in increased sca lp dihydrotestosterone levels, and possibly, acceleration of the balding pr ocess in genetically predisposed men and women.