Steroid 5-reductases and 3-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism
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Androgen action in mammals can be regulated at the pre-receptor level by the intracellular formation and degradation of potent androgens, such as 5-dihydrotestosterone (5-DHT).
In androgen target tissues (e.g. prostate), 5-DHT is formed from circulating testosterone by the action of the type 2 steroid 5-reductase (5-R) and its action is terminated by the action of a reductive 3-hydroxysteroid dehydrogenase (3-HSD) which forms the weak androgen 3-androstanediol.
Oxidative 3-HSD isoforms, however, can provide an alternative source of potent androgens by converting 3-androstanediol to 5-DHT.
Working in concert, 5-Rs and 3-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 5-R and reductive 3-HSD isoforms work consecutively to eliminate androgens and protect against hormone excess.
Thus, different 5-R and 3-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.