Pregnane-X-Receptor Controls Hepatic Glucuronidation During Pregnancy and Neonatal Development in Humanized UGT1 Mice
作者： Shujuan Chen , Mei-Fei Yueh , Ronald M. Evans , Robert H. Tukey
DOI: 10.1002/HEP.25671
关键词: Transgene 、 Small interfering RNA 、 Constitutive androstane receptor 、 Endocrinology 、 Gene silencing 、 Glucuronidation 、 Pregnane X receptor 、 Biology 、 Regulation of gene expression 、 Glucuronosyltransferase 、 Internal medicine
摘要: In humanized UDP glucuronosyltransferase-1 (hUGT1) mice that express the entire UGT1 locus, maternal hepatic UGT1A genes are dramatically induced 12-14 days after conception. Steroid induction of UGT1A1 gene indicates xenobiotic sensors, such as pregnane X receptor (PXR) and constitutive androstane (CAR), may underlie process. contrast, neonatal hUGT1 display severe hyperbilirubinemia, with limited expression genes. This study identifies PXR both a positive negative regulator gene. Pregnancy hormones, in particular glucocorticoids, target human glucuronidation. Employing reverse genetics, where has been genetically deleted, hUGT1/Pxr−/− show liver during pregnancy, whereas exact opposite occurs newborn mice. Neonatal delayed severely hyperbilirubinemic. However, mice, hyperbilirubinemia is greatly reduced due to UGT1A1. Thus, serves repress development. Transcriptional silencing was relieved hepatocytes through interruption by small interfering RNA. Conclusion: key pregnancy glucuronidation capacity addition modulating severity jaundice. (Hepatology 2012;56:658–667)
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