ArticleHepatology (Baltimore, Md.)2012
Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Posaconazole Target Attainment in Critically Ill Children: A 15-Year Single-Center Retrospective Analysis.Clinical and translational science · 2026Article
- Considerations for the Use of Long-Acting and Extended-Release Agents During Pregnancy and Lactation.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- An update on the physiologic changes during pregnancy and their impact on drug pharmacokinetics and pharmacogenomics.Journal of basic and clinical physiology and pharmacology · 2022Review
- Intestinal UDP-Glucuronosyltransferase 1A1 and Protection against Irinotecan-Induced Toxicity in a Novel UDP-Glucuronosyltransferase 1A1 Tissue-Specific Humanized Mouse Model.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes.Frontiers in pharmacology · 2022Article
- The Impact of Pregnancy on Antihypertensive Drug Metabolism and Pharmacokinetics: Current Status and Future Directions.Expert opinion on drug metabolism & toxicology · 2021Review
- Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia.Scientific reports · 2021Article
- Regulation of Intestinal UDP-Glucuronosyltransferase 1A1 by the Farnesoid X Receptor Agonist Obeticholic Acid Is Controlled by Constitutive Androstane Receptor through Intestinal Maturation.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Maternal-Fetal Pharmacology of Drugs: A Review of Current Status of the Application of Physiologically Based Pharmacokinetic Models.Frontiers in pediatrics · 2021Review
- Pregnancy-Related Hormones Increase UGT1A1-Mediated Labetalol Metabolism in Human Hepatocytes.Frontiers in pharmacology · 2021Article
- PharmGKB summary: lamotrigine pathway, pharmacokinetics and pharmacodynamics.Pharmacogenetics and genomics · 2020Review
- Differential Role of Liver X Receptor (LXR)Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Drugs in pregnancy: Pharmacologic and physiologic changes that affect clinical care.Seminars in perinatology · 2020Review
- NRF2-Independent Regulation of Intestinal Constitutive Androstane Receptor by the Pro-Oxidants Cadmium and Isothiocyanate inDrug metabolism and disposition: the biological fate of chemicals · 2020Article
- Experimental models assessing bilirubin neurotoxicity.Pediatric research · 2020Review
- Pharmacokinetics of HIV-Integrase Inhibitors During Pregnancy: Mechanisms, Clinical Implications and Knowledge Gaps.Clinical pharmacokinetics · 2019Review
- HumanizedDrug metabolism and disposition: the biological fate of chemicals · 2018Article
- Pharmacokinetic Changes during Pregnancy According to Genetic Variants: a Prospective Study in HIV-Infected Patients Receiving Atazanavir-Ritonavir.Antimicrobial agents and chemotherapy · 2018Article
- Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.Drug metabolism and pharmacokinetics · 2018Review
- Pregnancy Increases Norbuprenorphine Clearance in Mice by Induction of Hepatic Glucuronidation.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledIn humanized UDP glucuronosyltransferase-1 (hUGT1) mice that express the entire UGT1 locus, the maternal hepatic UGT1A genes are dramatically induced 12-14 days after conception. Steroid induction of the UGT1A1 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 hUGT1 mice display severe hyperbilirubinemia, with limited expression of the UGT1A genes. This study identifies PXR as both a positive and negative regulator of the UGT1A1 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, hUGT1/Pxr(-/-) mice show limited induction of the liver UGT1A genes during pregnancy, whereas the exact opposite occurs in newborn mice. Neonatal hUGT1 mice show delayed expression of hepatic UGT1A1 and are severely hyperbilirubinemic. However, in hUGT1/Pxr(-/-) mice, hyperbilirubinemia is greatly reduced due to induction of hepatic UGT1A1. Thus, PXR serves to repress UGT1A1 gene expression during development. Transcriptional silencing of the UGT1A1 gene was relieved in neonatal hUGT1 hepatocytes through interruption of PXR by small interfering RNA.
conclusionPXR is a key regulator of pregnancy induced glucuronidation capacity in addition to modulating the severity of neonatal jaundice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.