Molecular Biology Reports

, Volume 33, Issue 2, pp 91–96

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

Article

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 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.

Keywords

bilirubin cortisol GR HNF PXR UGT1A1 

Abbreviations

CAR

constitutive androstane receptor

EMSA

electrophretic mobility shift assay

GR

human glucocorticoid receptor

HNF

hepatocyte nuclear factor

PE

proximal element

PXR

human pregnenolone xenobiotic receptor

RIF

rifampicin

UGT

UDP-glucuronosyltransferase

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Evans, WE, Relling, MV 1999Science286487491PubMedCrossRefGoogle Scholar
  2. 2.
    King, C, Finley, B, Franklin, R 2000Drug Metab. Dispos.28661663PubMedGoogle Scholar
  3. 3.
    Ueyama, H, Koiwai, O, Soeda, Y, Sato, H, Satoh, Y, Ohkubo, I, Doida, Y 1997Hepatol. Res.9152163CrossRefGoogle Scholar
  4. 4.
    Sato, H, Koiwai, O, Tanabe, K, Kashiwamata, S 1990Biochem. Biophys. Res. Commun.169260264PubMedCrossRefGoogle Scholar
  5. 5.
    Sato, H, Adachi, Y, Koiwai, O 1996Lancet347578581CrossRefGoogle Scholar
  6. 6.
    Koiwai, O, Aono, S, Adachi, Y, Kamisaka, T, Yasui, Y, Nishizawa, M, Sato, H 1996Hum. Mol. Genet.5645647PubMedCrossRefGoogle Scholar
  7. 7.
    Peters, WHM, Jansen, PLM, Nauta, HM 1984J. Biol. Chem.2591179111705Google Scholar
  8. 8.
    Oguri, K 2000Xenobio. Metab. Dispos.15136142Google Scholar
  9. 9.
    Pascussi, JM, Dvorak, Z, Gerbal-Chaloin, S, Assenat, E, Maurel, P, Vilarem, MJ 2003Drug Metab. Rev.35255268PubMedCrossRefGoogle Scholar
  10. 10.
    Gong, QH, Cho, JW, Huang, T, Potter, C, Gholami, N, Basu, NK, Kubota, S, Carvalho, S, Pennington, MW, Owens, IS, Popescu, NC 2001Pharmacogenetics11357368PubMedCrossRefGoogle Scholar
  11. 11.
    Bosma, PJ, Chowdhury, JR, Bakker, C 1995N. Engl. J. Med.33311711175PubMedCrossRefGoogle Scholar
  12. 12.
    Monaghan, G, Ryan, M, Seddon, R, Hume, R, Burchell, B 1996Lancet347578581PubMedCrossRefGoogle Scholar
  13. 13.
    Sugatani, J, Nishitani, S, Yamakawa, K, Yoshinari, K, Sueyoshi, T, Negishi, M, Miwa, M 2005Mol. Pharmocol.67845455CrossRefGoogle Scholar
  14. 14.
    Kanou, M, Usui, T, Ueyama, H, Sato, H, Ohkubo, I, Mizutani, T 2004Mol. Biol. Rep.31151158PubMedCrossRefGoogle Scholar
  15. 15.
    Dutton, GJ 1978Annu. Rev. Pharmacol. Toxicol.181735PubMedCrossRefGoogle Scholar
  16. 16.
    Wishart, GJ, Dutton, GJ 1977Biochem. J.168507511PubMedGoogle Scholar
  17. 17.
    Wishart, GJ, Goheer, MA, Leakey, JE, Dutton, GJ 1977Biochem. J.166249253PubMedGoogle Scholar
  18. 18.
    Gerbal-Chaloin, S, Daujat, M, Pascussi, JM, Pichard-Garcia, L, Vilarem, MJ, Maurel, P 2002J. Biol. Chem.277209217PubMedCrossRefGoogle Scholar
  19. 19.
    Kumar, V, Green, S, Stack, G, Berry, M, Jin, JR, Chambon, P 1987Cell51941951PubMedCrossRefGoogle Scholar
  20. 20.
    Lehmann, JM, McKee, DD, Watson, MA, Willson, TM, Moore, JT, Kliewer, SA 1998J. Clin. Invest.10210161023PubMedCrossRefGoogle Scholar
  21. 21.
    Yueh, MF, Huang, YH, Chen, S, Nguyen, N, Yukey, RH 2003J. Biol. Chem.2781500115006PubMedCrossRefGoogle Scholar
  22. 22.
    Xie, W, Yueh, MF, Radominska-Pnadya, A, Saini, SP, Negishi, M, Bottroff, BS, Cabrera, GY, Tuken, RH, Evans, RM 2003Proc. Natl. Acad. Sci. USA10041504156PubMedCrossRefGoogle Scholar
  23. 23.
    Huang, W, Zhang, J, Chua, SS, Qayanani, M, Han, Y, Granata, R, Moore, DD 2003Proc. Natl. Acad. Sci. USA10041564161PubMedCrossRefGoogle Scholar
  24. 24.
    Pascussi, JM, Drocourt, L, Fabre, JM, Maurel, P, Vilarem, MJ 2000Mol. Pharmacol.58361372PubMedGoogle Scholar
  25. 25.
    Faust, DM, Catherin, AM, Barbaux, S, Belkadi, L, Imaizumi-Scherrer, T, Weiss, MC 1996Mol. Cell. Biol.1631253137PubMedGoogle Scholar
  26. 26.
    Suh, DS, Rechier, MM 1997Mol. Endocrinol.1118221831PubMedCrossRefGoogle Scholar
  27. 27.
    Bernard, P, Goudonnet, H, Artur, Y, Desvergne, B, Wahli, W 1999Mol. Pharmacol.56526536PubMedGoogle Scholar
  28. 28.
    Pontoglio, M, Barra, J, Hadchouel, M, Doyen, A, Kress, C, Bach, JP, Babinet, C, Yaniv, M 1966Cell84575585CrossRefGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

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

Personalised recommendations