TY - JOUR
T1 - Expression and induction of CYP3As in human fetal hepatocytes
AU - Matsunaga, Tamihide
AU - Maruyama, Masataka
AU - Harada, Eri
AU - Katsuyama, Yoshihiko
AU - Sugihara, Nobuhiro
AU - Ise, Hirohiko
AU - Negishi, Naoki
AU - Ikeda, Uichi
AU - Ohmori, Shigeru
N1 - Funding Information:
This work was partly supported by Grants-in-Aid from the Ministry of Education, Culture, Sports and Science of Japan, and by the Matsuko Foundation.
PY - 2004/5/28
Y1 - 2004/5/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2004.04.041
DO - 10.1016/j.bbrc.2004.04.041
M3 - Article
C2 - 15120618
AN - SCOPUS:2142821390
SN - 0006-291X
VL - 318
SP - 428
EP - 434
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -