期刊
REPRODUCTION FERTILITY AND DEVELOPMENT
卷 24, 期 3, 页码 425-437出版社
CSIRO PUBLISHING
DOI: 10.1071/RD11159
关键词
cortisol; cytochrome P450; hepatocyte nuclear factor 4 alpha; mRNA expression; RT-PCR; sheep liver; western blot
资金
- CIHR
- IWRH
Cytochrome P450 (CYP) enzymes are important for the metabolism of many drugs. While there is information on their identity and ontogeny in humans and rodents, similar data in sheep are lacking. In the present study, cDNA sequences of several CYP enzymes (CYP2A6, CYP2C19, CYP2D6) were cloned by rapid amplification of cDNA ends. In adult, newborn and fetal sheep the mRNA and protein levels of these CYPs and the regulatory factor, hepatic nuclear factor 4 alpha (HNF4 alpha) were determined in liver samples using real-time PCR and western blotting. The effect of antenatal glucocorticoid on these enzymes was also studied by i.v. infusion of cortisol (0.45 mg h(-1); 80 h) to another group of fetuses. The mRNA and protein levels of the CYPs and HNF4 alpha were low or absent in the fetus, followed by increasing levels in the newborn and adult. Fetal cortisol administration significantly increased the mRNA and protein levels of CYP2D6. Moreover, the correlation observed between the CYP and HNF4 alpha mRNA levels suggests a possible regulatory role for this transcription factor. The findings suggest that fetal and newborn lambs have a low ability to metabolise drugs that are substrates of these enzymes, and that this ability increases with advancing postnatal age, similar to the situation in humans.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据