Altered cytochrome P450 expression in mice during pregnancy

Kwi Hye Koh, Hui Xie, Aiming Yu, Hyunyoung Jeong

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)165-169
Number of pages5
JournalDrug Metabolism and Disposition
Volume39
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Fingerprint

Cytochrome P-450 Enzyme System
Pregnancy
Protein Isoforms
Peroxisome Proliferator-Activated Receptors
Liver
Pharmaceutical Preparations
Postpartum Period
Real-Time Polymerase Chain Reaction
Theoretical Models
Down-Regulation
Messenger RNA

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Altered cytochrome P450 expression in mice during pregnancy. / Koh, Kwi Hye; Xie, Hui; Yu, Aiming; Jeong, Hyunyoung.

In: Drug Metabolism and Disposition, Vol. 39, No. 2, 02.2011, p. 165-169.

Research output: Contribution to journalArticle

Koh, Kwi Hye ; Xie, Hui ; Yu, Aiming ; Jeong, Hyunyoung. / Altered cytochrome P450 expression in mice during pregnancy. In: Drug Metabolism and Disposition. 2011 ; Vol. 39, No. 2. pp. 165-169.
@article{f34a6742980a4e6d8d186fc0e350890b,
title = "Altered cytochrome P450 expression in mice during pregnancy",
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.",
author = "Koh, {Kwi Hye} and Hui Xie and Aiming Yu and Hyunyoung Jeong",
year = "2011",
month = "2",
doi = "10.1124/dmd.110.035790",
language = "English (US)",
volume = "39",
pages = "165--169",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Altered cytochrome P450 expression in mice during pregnancy

AU - Koh, Kwi Hye

AU - Xie, Hui

AU - Yu, Aiming

AU - Jeong, Hyunyoung

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79251531656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251531656&partnerID=8YFLogxK

U2 - 10.1124/dmd.110.035790

DO - 10.1124/dmd.110.035790

M3 - Article

VL - 39

SP - 165

EP - 169

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 2

ER -