Regulation of endobiotics glucuronidation by ligand-activated transcription factors: physiological function and therapeutic potential

Drug Metab Rev. 2010 Feb;42(1):110-22. doi: 10.3109/03602530903219220.


Recent progresses in molecular pharmacology approaches have allowed the identification and characterization of a series of nuclear receptors (NR) which efficiently control the level UDP-glucuronosyltransferase (UGT) genes expression. These regulatory processes ensure optimized UGT expression in response to specific endogenous and/or exogenous stimuli. Interestingly, numerous endogenous activators of these NRs are conjugated by the UGT enzymes they regulate. In such a case, the NR-dependent regulation of UGT genes corresponds to a feedforward/feedback mechanism by which a bioactive molecule controls its own concentrations. In the present review, we will discuss i) how bilirubin reduces its circulating levels by activating AhR in the liver; ii) how bile acids modulate their hepatic glucuronidation via PXR- and FXR-dependent processes in enterohepatic tissues; and iii) how androgens inhibit their cellular metabolism in prostate cancer cells through an AR-dependent mechanism. Subsequently, with further discussion of the same examples (bilirubin and bile acids), we will illustrate how NR-dependent regulation of UGT enzymes may contribute to the beneficial effects of pharmacological activators of nuclear receptors, such as CAR and PPARa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activating Transcription Factors / metabolism
  • Activating Transcription Factors / physiology*
  • Bile Acids and Salts / metabolism*
  • Bilirubin / blood*
  • Cells, Cultured
  • Glucuronides / metabolism
  • Glucuronosyltransferase / metabolism
  • Liver / metabolism*
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Signal Transduction / physiology


  • Activating Transcription Factors
  • Bile Acids and Salts
  • Glucuronides
  • Receptors, Cytoplasmic and Nuclear
  • Glucuronosyltransferase
  • Bilirubin