Steroidogenic enzymes in skin.
The gonadal synthesis of testosterone from cholesterol involves four enzymes, namely, 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 is 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 the androgen responsible for a process leading to androgenetic alopecia. Consequently, the 5a-reductase inhibitor finasteride was developed and has proven efficacious in promoting hair growth as a consequence of lowering scalp and plasma dihydrotestosterone levels. In contrast to the direct synthesis of dihydrotestosterone from testosterone, biologically inactive C19-steroids produced by glandular and peripheral tissues may also feed into the scalp skin production of dihydrotestosterone by the local expression of reductive 17b-hydroxysteroid dehydrogenase, oxidative 3a-hydroxysteroid dehydrogenase, and 3b-hydroxysteroid dehydrogenase enzymes. Aberrant expression of one or more of these enzymes, could conceivably result in increased scalp dihydrotestosterone levels, and possibly, acceleration of the balding process in genetically predisposed men and women.
Andersson
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Department of Obstetrics-Gynecology and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032, USA. stefan.andersson@UTSouthwestern.edu
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000505:Alopecia / Q000201:enzymology*; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D012867:Skin / Q000201:enzymology*
D013196:Dihydrotestosterone; D006913:Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase