Altered cytochrome P450 expression in mice during pregnancy.
Human pregnancy is known to influence hepatic drug metabolism in a cytochrome (P450)-specific manner. However, the underlying mechanisms remain unknown, in part due to a lack of experimental models to study altered drug metabolism during pregnancy. In this study, we examined how pregnancy influences expression of major P450 isoforms in mice. Liver tissues were isolated from female FVB/N-mice at different gestational time points: prepregnancy, 7, 14, and 21 days of pregnancy, and 7 days postpartum. mRNA expression levels of major P450 isoforms (Cyp1a2, Cyp2a5, Cyp2b10, Cyp2c37, Cyp2d22, Cyp2e1, Cyp3a11, and Cyp3a41) in the liver tissues were determined by quantitative real-time polymerase chain reaction. Whereas Cyp2a5 expression was unchanged, Cyp3a41 expression was significantly increased during pregnancy. In contrast, expression of Cyp1a2, Cyp2c37, Cyp2d22, Cyp2e1, and Cyp3a11 was decreased. Expression of Cyp2d22 and Cyp2e1 isoforms correlated with that of peroxisome proliferator-activated receptor (PPAR)α in the mouse livers, suggesting potential involvement of PPARα in down-regulation of the P450 expression during pregnancy. Effects of pregnancy on expression of other P450 mouse isoforms as well as on in vivo drug disposition remain to be characterized. These results provide a guide for future studies on P450 regulation during pregnancy.
Koh
Kwi Hye
KH
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA. yjeong@uic.edu
Xie
Hui
H
Yu
Ai-Ming
AM
Jeong
Hyunyoung
H
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D007527:Isoenzymes; D008099:Liver / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
D016207:Cytokines; D007527:Isoenzymes; D012333:RNA, Messenger; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System