Steroid 5 alpha-reductases and 3 alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism

Androgen action in mammals can be regulated at the pre-receptor level by th e intracellular formation and degradation of potent androgens, such as 5 al pha -dihydrotestosterone (5 alpha -DHT). In androgen target tissues (e.g. p rostate), 5 alpha -DHT is formed from circulating testosterone by the actio n of the type 2 steroid 5 alpha -reductase (5 alpha -R) and its action is t erminated by the action of a reductive 3 alpha -hydroxysteroid dehydrogenas e (3 alpha -HSD) which forms the weak androgen 3 alpha -androstanediol. Oxi dative 3a-HSD isoforms, however, can provide an alternative source of poten t androgens by converting 3 alpha -androstanediol to 5 alpha -DHT. Working in concert, 5 alpha -Rs and 3 alpha -HSDs determine the amount and the type of androgen available for the androgen receptor and hence affect transcrip tion of genes under androgen control. In peripheral tissues (e.g. liver), t ype I 5 alpha -R and reductive 3 alpha -HSD isoforms work consecutively to eliminate androgens and protect against hormone excess. Thus, different 5 a lpha -R and 3 alpha -HSD isoforms participate in distinct anabolic and cata bolic processes and their important roles in androgen action render them dr ug targets for the treatment of androgen-dependent diseases.