PT  - JOURNAL ARTICLE
AU  - Su-Young Choi
AU  - Kwi Hye Koh
AU  - Hyunyoung Jeong
TI  - Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone
AID  - 10.1124/dmd.112.046276
DP  - 2013 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 263--269
VI  - 41
IP  - 2
4099  - http://dmd.aspetjournals.org/content/41/2/263.short
4100  - http://dmd.aspetjournals.org/content/41/2/263.full
SO  - Drug Metab Dispos2013 Feb 01; 41
AB  - Results from clinical studies suggest that pregnancy alters hepatic drug metabolism in a cytochrome P450 (P450) isoform-specific manner, and rising concentrations of female hormones are potentially responsible for the changes. The objective of this study was to comprehensively characterize the effects of estrogen and progesterone on the expression and activity of major drug-metabolizing P450s. To this end, primary human hepatocytes were treated with estradiol and progesterone, and mRNA expression and activity levels of 10 different P450 isoforms were determined. The results showed that estradiol enhances CYP2A6, CYP2B6, and CYP3A4 expression, whereas progesterone induces CYP2A6, CYP2B6, CYP2C8, CYP3A4, and CYP3A5 expression. The induction was mainly observed when the average hormone concentrations were at the levels reached during pregnancy, suggesting that these effects are likely pregnancy-specific. Estradiol also increased enzyme activities of CYP2C9 and CYP2E1 without affecting the mRNA expression levels by unknown mechanisms. Taken together, our results show differential effects of estrogen and progesterone on P450 expression, suggesting involvement of different regulatory mechanisms in female hormone-mediated P450 regulation. Our findings potentially provide a basis in mechanistic understanding for altered drug metabolism during pregnancy.