{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:54:52Z","timestamp":1789167292160,"version":"build-2803163510"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T00:00:00Z","timestamp":1339372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:sec><jats:title\/><jats:p><jats:bold>In humanized UDP glucuronosyltransferase-1 (<\/jats:bold><jats:bold>hUGT1<\/jats:bold><jats:bold>) mice that express the entire<\/jats:bold><jats:bold>UGT1<\/jats:bold><jats:bold>locus, the maternal hepatic<\/jats:bold><jats:bold>UGT1A<\/jats:bold><jats:bold>genes are dramatically induced 12-14 days after conception. Steroid induction of the<\/jats:bold><jats:bold>UGT1A1<\/jats:bold><jats:bold>gene indicates that xenobiotic sensors, such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), may underlie the induction process. In contrast, neonatal<\/jats:bold><jats:bold>hUGT1<\/jats:bold><jats:bold>mice display severe hyperbilirubinemia, with limited expression of the<\/jats:bold><jats:bold>UGT1A<\/jats:bold><jats:bold>genes. This study identifies PXR as both a positive and negative regulator of the<\/jats:bold><jats:bold>UGT1A1<\/jats:bold><jats:bold>gene. Pregnancy hormones, in particular the glucocorticoids, target PXR as a positive regulator of human glucuronidation. Employing reverse genetics, where PXR has been genetically deleted,<\/jats:bold><jats:bold>hUGT1\/Pxr<\/jats:bold><jats:bold>\u2212\/\u2212 mice show limited induction of the liver<\/jats:bold><jats:bold>UGT1A<\/jats:bold><jats:bold>genes during pregnancy, whereas the exact opposite occurs in newborn mice. Neonatal<\/jats:bold><jats:bold>hUGT1<\/jats:bold><jats:bold>mice show delayed expression of hepatic UGT1A1 and are severely hyperbilirubinemic. However, in<\/jats:bold><jats:bold>hUGT1\/Pxr<\/jats:bold><jats:bold>\u2212\/\u2212 mice, hyperbilirubinemia is greatly reduced due to induction of hepatic UGT1A1. Thus, PXR serves to repress<\/jats:bold><jats:bold>UGT1A1<\/jats:bold><jats:bold>gene expression during development. Transcriptional silencing of the<\/jats:bold><jats:bold>UGT1A1<\/jats:bold><jats:bold>gene was relieved in neonatal<\/jats:bold><jats:bold>hUGT1<\/jats:bold><jats:bold>hepatocytes through interruption of PXR by small interfering RNA.<\/jats:bold><jats:bold>Conclusion<\/jats:bold><jats:bold>: PXR is a key regulator of pregnancy induced glucuronidation capacity in addition to modulating the severity of neonatal jaundice. (HEPATOLOGY 2012)<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/hep.25671","type":"journal-article","created":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T05:16:47Z","timestamp":1330406207000},"page":"658-667","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice"],"prefix":"10.1097","volume":"56","author":[{"given":"Shujuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Fei","family":"Yueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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