Induction of human UDP-glucuronosyltransferase 1A1 by cortisol-GR

Molecular Biology Reports
Toru UsuiTakaharu Mizutani

Abstract

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 microM, a major natural cortico-steroid, with human glucocorticoid receptor (GR). RU486 of a typical GR antagonist at 10 microM 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 ...Continue Reading

References

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Citations

Feb 13, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shingo OdaMiki Nakajima
Apr 10, 2020·Expert Opinion on Drug Metabolism & Toxicology·Megan NearyAdeniyi Olagunju
Mar 22, 2016·European Journal of Clinical Investigation·Jorien Werumeus BuningRobin P F Dullaart
Dec 31, 2009·Journal of Environmental and Public Health·Takaharu Mizutani
Jul 15, 2020·Antimicrobial Agents and Chemotherapy·Yi ZhengJade Ghosn

Related Concepts

UGT1A1 protein, human
DNA Sequence
Drug Antagonism
Glucocorticoid Effect
Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer
Early Promoters, Genetic
Glucocorticoid Receptor
Receptors, Steroid
Transfection
UDP-Glucuronic Acid 3-O-beta-D-Galactosyl-D-Galactose Glucuronosyltransferase

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