Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans
Alain Bélanger, Georges Pelletier, Fernand Labrie, Olivier Barbier and Sarah Chouinard
Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Laval University, Québec, G1V 4G2, Canada
Available online 23 October 2003.
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In humans, 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-HSD and 5α-reductase activities in androgen target tissues, such as the prostate and skin, convert dehydroepiandrosterone, androstenedione and testosterone into the most potent natural androgen dihydrotestosterone (DHT). This androgen is converted mainly in situ into two phase I metabolites, androsterone (ADT) and androstane-3α,17β-diol (3α-DIOL), which might be back converted to DHT. Here, we discuss the recent findings regarding the characterization of specific UDP-glucuronosyltransferases (UGTs), UGT2B7, B15 and B17, responsible for the glucuronidation of these metabolites. The tissue distribution and cellular localization of the UGT2B transcripts and proteins in humans clearly indicate that these enzymes are synthesized in androgen-sensitive tissues. It is postulated that the conjugating activity of UGT enzymes is the main mechanism for modulating the action of steroids and protecting the androgen-sensitive tissues from deleteriously high concentrations of DHT, ADT and 3α-DIOL.
- UGT enzymes
- UGT2B enzymes in the human prostate
- UGT2B15 and prostate cancer
- UGT2B enzymes in the human skin
Figure 1. Enzymes involved in metabolism of androgens in peripheral intracrine tissues [6, 10, 11, 12 and 13]. Dehydroepiandrosterone, its sulfate, androst-5-ene-3β,17β-diol and its sulfate, and androstenedione are secreted by the adrenals, whereas testosterone is produced by the testes. Abbreviations: HSD, hydroxy steroid dehydrogenase; HSE, hydroxysteroid epimerase; RODH, retinoldehydrogenase; 1, the enzyme has not been isolated so far.
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