Molecular Biology Reports

, Volume 33, Issue 2, pp 91–96

Induction of Human UDP-glucuronosyltransferase 1A1 by Cortisol-GR


DOI: 10.1007/s11033-005-1750-9

Cite this article as:
Usui, T., Kuno, T. & Mizutani, T. Mol Biol Rep (2006) 33: 91. doi:10.1007/s11033-005-1750-9


During the course of the study of UGT1A1 induction by bilirubin, we could not detect the induction of the reporter gene (−3174/+14) of human UGT1A1 in HepG2 by bilirubin (Mol. Biol. Rep. 31: 151–158 (2004)). In this report, we show the finding of the induction of the reporter gene of UGT1A1 by cortisol at 1 μM, a major natural cortico-steroid, with human glucocorticoid receptor (GR). RU486 of a typical GR antagonist at 10 μM inhibited the induction by cortisol from 5.9- to 1.8-fold. This result indicates that the induction by cortisol-GR is dependence on ligand-binding. This induction is caused by the UGT reporter gene itself, from the results of noinduction with control vector pGL2 (equal to pGV-C) in the presence of cortisol-GR. We confirmed that the induction of the reporter gene by cortisol is dependent on the position of proximal element (−97/−53) of UGT1A1. From this result, we concluded that the increase of corticosteroid in neonates must induce the elevation of UGT1A1 after birth and prevent jaundice. With the study of induction by corisol, we studied the influence of co-expression of PXR (pregnenolone xenobiotic receptor) with the UGT1A1 reporter gene and we could not find the induction of UGT1A1 expression in the presence of dexamethasone, rifampicin, or pregnenolone 16α-carbonitrile of the PXR ligands. These results suggest that the induction of UGT1A1 expression by GR is not mediated by PXR, unlike the induction of CYP3A4 through PXR.


bilirubin cortisol GR HNF PXR UGT1A1 



constitutive androstane receptor


electrophretic mobility shift assay


human glucocorticoid receptor


hepatocyte nuclear factor


proximal element


human pregnenolone xenobiotic receptor





Copyright information

© Springer 2006

Authors and Affiliations

  1. 1.Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical SciencesNagoya City UniversityNagoyaJapan

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