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Rapid CommunicationShort Communication

Altered Cytochrome P450 Expression in Mice during Pregnancy

Kwi Hye Koh, Hui Xie, Ai-Ming Yu and Hyunyoung Jeong
Drug Metabolism and Disposition February 2011, 39 (2) 165-169; DOI: https://doi.org/10.1124/dmd.110.035790
Kwi Hye Koh
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Hui Xie
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Ai-Ming Yu
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Hyunyoung Jeong
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Abstract

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.

Footnotes

  • This work was supported in part by the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant HD055313]; the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant K12-HD055892] (fellowship to H.J.); and the National Institutes of Health National Center for Research Resources [Grant UL1-RR029879] (to H.X.).

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.110.035790.

  • ABBREVIATIONS:

    P450
    cytochrome P450
    IL
    interleukin
    TNF
    tumor necrosis factor
    IFN
    interferon
    PXR
    pregnane X receptor
    CAR
    constitutive androstane receptor
    qRT-PCR
    quantitative real-time polymerase chain reaction
    CT
    cycle threshold
    ANOVA
    analysis of variance
    PPAR
    peroxisome proliferator-activated receptor
    AhR
    Aryl hydrocarbon receptor
    ER
    estrogen receptor
    WY-14,643
    4-chloro-6-(2,3-xylidino)-2-pyrimidinyl)thioacetic acid.

  • Received August 14, 2010.
  • Accepted October 22, 2010.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 39 (2)
Drug Metabolism and Disposition
Vol. 39, Issue 2
1 Feb 2011
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Rapid CommunicationShort Communication

Altered Cytochrome P450 Expression in Mice during Pregnancy

Kwi Hye Koh, Hui Xie, Ai-Ming Yu and Hyunyoung Jeong
Drug Metabolism and Disposition February 1, 2011, 39 (2) 165-169; DOI: https://doi.org/10.1124/dmd.110.035790

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Altered Cytochrome P450 Expression in Mice during Pregnancy

Kwi Hye Koh, Hui Xie, Ai-Ming Yu and Hyunyoung Jeong
Drug Metabolism and Disposition February 1, 2011, 39 (2) 165-169; DOI: https://doi.org/10.1124/dmd.110.035790
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