Expression and induction of CYP3As in human fetal hepatocytes

Tamihide Matsunaga, Masataka Maruyama, Eri Harada, Yoshihiko Katsuyama, Nobuhiro Sugihara, Hirohiko Ise, Naoki Negishi, Uichi Ikeda, Shigeru Ohmori

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34 Citations (Scopus)

Abstract

CYP3A4 and CYP3A7 mRNA expression levels were markedly up-regulated by dexamethasone (DEX), but not by rifampicin (RIF). CYP3A5 mRNA level was not increased significantly by DEX, RIF, or phenobarbital. Testosterone 6β-hydroxylase activity was induced to about 2-fold of control by DEX. However, concomitant treatment with RIF did not alter DEX-mediated induction of CYP3A mRNA expression and testosterone 6β-hydroxylase activity. DEX-mediated induction of CYP3A mRNA was suppressed in a dose-dependent manner by RU486, a glucocorticoid receptor (GR) antagonist. At 5μM RU486, DEX-mediated induction of CYP3A4, CYP3A5, and CYP3A7 mRNA expression was inhibited almost completely. These results suggest that, in human fetal hepatocytes, PXR is not involved in DEX-mediated induction of CYP3A4 and CYP3A7, and that the induction is mediated directly by GR.

Original languageEnglish
Pages (from-to)428-434
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number2
DOIs
Publication statusPublished - May 28 2004

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Matsunaga, T., Maruyama, M., Harada, E., Katsuyama, Y., Sugihara, N., Ise, H., Negishi, N., Ikeda, U., & Ohmori, S. (2004). Expression and induction of CYP3As in human fetal hepatocytes. Biochemical and Biophysical Research Communications, 318(2), 428-434. https://doi.org/10.1016/j.bbrc.2004.04.041