Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells.

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Matsunaga T, Maruyama M, Matsubara T, Nagata K, Yamazoe Y, Ohmori S

Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells.

Drug Metab Pharmacokinet. 2012;27(6):653-7. doi: 10.2133/dmpk.dmpk-12-nt-018. Epub 2012 May 22.

PubMed ID

22673009 [ View in PubMed

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Abstract

Human fetal liver (HFL) cells express major drug metabolic enzymes CYP3A4, CYP3A5 and CYP3A7. In the fetal hepatocytes, betamethasone and dexamethasone (DEX) markedly enhanced the expression levels of CYP3A4 and CYP3A7 mRNAs and slightly increased the expression level of CYP3A5 mRNA. Interestingly, a high correlation between the CYP3A induction ability and the intensity of anti-inflammatory effect was observed. Human glucocorticoid receptor (GR)-small interfering RNA clearly attenuated the expression level of GR mRNA, and diminished the DEX-stimulated CYP3A4, CYP3A5 and CYP3A7 expression in HFL cells. These findings indicate that GR mediates the induction of CYP3A4 and CYP3A7 expression in human fetal hepatocytes as well as the CYP3A5.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Betamethasone	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inducer	Details
Betamethasone	Cytochrome P450 3A5	Protein	Humans	Unknown	Inducer	Details
Betamethasone	Cytochrome P450 3A7	Protein	Humans	Unknown	Not Available	Details