Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans

Trends Endocrinol Metab. 2003 Dec;14(10):473-9. doi: 10.1016/j.tem.2003.10.005.

Abstract

In humans, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-HSD and 5alpha-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-3alpha,17beta-diol (3alpha-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 3alpha-DIOL.

Publication types

  • Review

MeSH terms

  • Androgens / metabolism*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Prostate / metabolism
  • Prostatic Neoplasms / metabolism
  • Skin / metabolism

Substances

  • Androgens
  • Isoenzymes
  • Glucuronosyltransferase