Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism.
Androgen action in mammals can be regulated at the pre-receptor level by the intracellular formation and degradation of potent androgens, such as 5alpha-dihydrotestosterone (5alpha-DHT). In androgen target tissues (e.g. prostate), 5alpha-DHT is formed from circulating testosterone by the action of the type 2 steroid 5alpha-reductase (5alpha-R) and its action is terminated by the action of a reductive 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) which forms the weak androgen 3alpha-androstanediol. Oxidative 3alpha-HSD isoforms, however, can provide an alternative source of potent androgens by converting 3alpha-androstanediol to 5alpha-DHT. Working in concert, 5alpha-Rs and 3alpha-HSDs determine the amount and the type of androgen available for the androgen receptor and hence affect transcription of genes under androgen control. In peripheral tissues (e.g. liver), type 1 5alpha-R and reductive 3alpha-HSD isoforms work consecutively to eliminate androgens and protect against hormone excess. Thus, different 5alpha-R and 3alpha-HSD isoforms participate in distinct anabolic and catabolic processes and their important roles in androgen action render them drug targets for the treatment of androgen-dependent diseases.
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Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA, 19104-6084, USA.
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D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000728:Androgens / Q000378:metabolism*; D000818:Animals; D006801:Humans
D000728:Androgens; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase