Autoimmune, Cholestatic and Biliary Disease

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Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice†

  1. Shujuan Chen1,
  2. Mei-Fei Yueh1,
  3. Ronald M. Evans2,
  4. Robert H. Tukey1,3,‡,*

Article first published online: 11 JUN 2012

DOI: 10.1002/hep.25671

Issue

Hepatology

Hepatology

Volume 56, Issue 2, pages 658–667, August 2012

Additional Information

How to Cite

Chen, S., Yueh, M.-F., Evans, R. M. and Tukey, R. H. (2012), Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice. Hepatology, 56: 658–667. doi: 10.1002/hep.25671

Author Information

  1. 1

    Department of Pharmacology, Laboratory of Environmental Toxicology, University of California, San Diego, La Jolla, CA

  2. 2

    Howard Hughes Medical Institute and Gene Expression Laboratory, Salk Institute of Biological Studies, La Jolla, CA

  3. 3

    Department of Chemistry & Biochemistry, Laboratory of Environmental Toxicology, University of California, San Diego, La Jolla, CA

  1. ‡

    fax: 858-822-0363

*Department of Pharmacology, and Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive MC 0722, La Jolla, CA 92093-0722

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    fax: 858-822-0363

Publication History

  1. Issue published online: 25 JUL 2012
  2. Article first published online: 11 JUN 2012
  3. Accepted manuscript online: 28 FEB 2012 12:14AM EST
  4. Manuscript Accepted: 13 FEB 2012
  5. Manuscript Received: 29 AUG 2011

Funded by

  • United States Public Health Service. Grant Number: GM086713
  • Superfund Research Program. Grant Number: P42ES010337

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References

  • 1
    Blumberg B, Sabbagh W Jr, Juguilon H, Bolado J Jr, van Meter CM, Ong ES, et al. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 1998; 12: 3195-3205.
  • 2
    Xie W, Evans RM. Orphan nuclear receptors: the exotics of xenobiotics. J Biol Chem 2001; 276: 37739-37742.
  • 3
    Xie W, Yeuh MF, Radominska-Pandya A, Saini SPS, Negishi Y, Bottroff BS, et al. Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc Natl Acad Sci U S A 2003; 100: 4150-4155.
  • 4
    Kawamoto T, Kakizaki S, Yoshinari K, Negishi M. Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. Mol Endocrinol 2000; 14: 1897-1905.
  • 5
    Timsit YE, Negishi M. CAR and PXR: the xenobiotic-sensing receptors. Steroids 2007; 72: 231-246.
  • 6
    Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude ER, Chowdhury JR, et al. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 1994; 269: 17960-17964.
  • 7
    Bacq Y, Zarka O, Brechot JF, Mariotte N, Vol S, Tichet J, et al. Liver function tests in normal pregnancy: a prospective study of 103 pregnant women and 103 matched controls. HEPATOLOGY 1996; 23: 1030-1034.
    Direct Link:
  • 8
    Jeong H, Choi S, Song JW, Chen H, Fischer JH. Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica 2008; 38: 62-75.
  • 9
    Harden CL. Pregnancy effects on lamotrigine levels. Epilepsy Curr 2002; 2: 183.
    Direct Link:
  • 10
    Chen H, Yang K, Choi S, Fischer JH, Jeong H. Up-regulation of UDP-glucuronosyltransferase (UGT) 1A4 by 17beta-estradiol: a potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metab Dispos 2009; 37: 1841-1847.
  • 11
    Boo NY, Wong FL, Wang MK, Othman A. Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia. Pediatr Int 2009; 51: 488-493.
    Direct Link:
  • 12
    Kawade N, Onishi S. The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver. Biochem J 1981; 196: 257-260.
  • 13
    Coughtrie MW, Burchell B, Leakey JE, Hume R. The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isoenzymes in rat and human liver microsomes. Mol Pharmacol 1988; 34: 729-735.
  • 14
    Chen S, Beaton D, Nguyen N, Senekeo-Effenberger K, Brace-Sinnokrak E, Argikar U, et al. Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem 2005; 280: 37547-37557.
  • 15
    Fujiwara R, Nguyen N, Chen S, Tukey RH. Developmental hyperbilirubinemia and CNS toxicity in mice humanized with the UDP glucuronosyltransferase 1 (UGT1) locus. Proc Natl Acad Sci U S A 2010; 107: 5024-5029.
  • 16
    Nguyen N, Bonzo JA, Chen S, Chouinard S, Kelner M, Hardiman G, et al. Disruption of the Ugt1 locus in mice resembles human Crigler-Najjar type I disease. J Biol Chem 2008; 283: 7901-7911.
  • 17
    Xie W, Barwick JL, Downes M, Blumberg B, Simon CM, Nelson MC, et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 2000; 406: 435-439.
  • 18
    Strassburg CP, Oldhafer K, Manns MP, Tukey RH. Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue. Mol Pharmacol 1997; 52: 212-220.
  • 19
    Okino ST, Quattrochi LC, Pookot D, Iwahashi M, Dahiya R. A dioxin-responsive enhancer 3′ of the human CYP1A2 gene. Mol Pharmacol 2007; 72: 1457-1465.
  • 20
    Albert C, Vallee M, Beaudry G, Belanger A, Hum DW. The monkey and human uridine diphosphate-glucuronosyltransferase UGT1A9, expressed in steroid target tissues, are estrogen-conjugating enzymes. Endocrinology 1999; 140: 3292-3302.
  • 21
    Wilson MD, Odom DT. Evolution of transcriptional control in mammals. Curr Opin Genet Dev 2009; 19: 579-585.
  • 22
    Prud'homme B, Gompel N, Carroll SB. Emerging principles of regulatory evolution. Proc Natl Acad Sci U S A 2007; 104( Suppl 1): 8605-8612.
  • 23
    Jeong H, Choi S, Song JW, Chen H, Fischer JH. Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica 2008; 38: 62-75.
  • 24
    Blumberg B, Kang H, Bolado J Jr, Chen H, Craig AG, Moreno TA, et al. BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites. Genes Dev 1998; 12: 1269-1277.
  • 25
    Moore JT, Kliewer SA. Use of the nuclear receptor PXR to predict drug interactions. Toxicology 2000; 153: 1-10.
  • 26
    Sugatani J, Nishitani S, Yamakawa K, Yoshinari K, Sueyoshi T, Negishi M, et al. Transcriptional regulation of human UGT1A1 gene expression: activated glucocorticoid receptor enhances constitutive androstane receptor/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting protein 1. Mol Pharmacol 2005; 67: 845-855.
  • 27
    Wagner M, Halilbasic E, Marschall HU, Zollner G, Fickert P, Langner C, et al. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. HEPATOLOGY 2005; 42: 420-430.
    Direct Link:
  • 28
    Chen C, Staudinger JL, Klaassen CD. Nuclear receptor, pregname X receptor, is required for induction of UDP-glucuronosyltranferases in mouse liver by pregnenolone-16 alpha-carbonitrile. Drug Metab Dispos 2003; 31: 908-915.
  • 29
    Wilson MD, Barbosa-Morais NL, Schmidt D, Conboy CM, Vanes L, Tybulewicz VL, et al. Species-specific transcription in mice carrying human chromosome 21. Science 2008; 322: 434-438.
  • 30
    Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, et al. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 2007; 39: 730-732.
  • 31
    Brites D, Fernandes A, Falcao AS, Gordo AC, Silva RF, Brito MA. Biological risks for neurological abnormalities associated with hyperbilirubinemia. J Perinatol 2009; 29( Suppl 1): S8-S13.
  • 32
    Watchko JF, Lin Z. Exploring the genetic architecture of neonatal hyperbilirubinemia. Semin Fetal Neonatal Med 2010; 15: 169-175.
  • 33
    Valaes T, Kipouros K, Petmezaki S, Solman M, Doxiadis SA. Effectiveness and safety of prenatal phenobarbital for the prevention of neonatal jaundice. Pediatr Res 1980; 14: 947-952.
  • 34
    Murki S, Dutta S, Narang A, Sarkar U, Garewal G. A randomized, triple-blind, placebo-controlled trial of prophylactic oral phenobarbital to reduce the need for phototherapy in G6PD-deficient neonates. J Perinatol 2005; 25: 325-330.
  • 35
    Arya VB, Agarwal R, Paul VK, Deorari AK. Efficacy of oral phenobarbitone in term “at risk” neonates in decreasing neonatal hyperbilirubinemia: a randomized double-blinded, placebo controlled trial. Indian Pediatr 2004; 41: 327-332.
  • 36
    Allen JW, Tommarello S, Carcillo J, Hansen TW. Effects of endotoxemia and sepsis on bilirubin oxidation by rat brain mitochondrial membranes. Biol Neonate 1998; 73: 340-345.
  • 37
    Madarek EO, Najati N. The effect of glucocorticoid therapy in preventing early neonatal complications in preterm delivery. J Perinat Med 2003; 31: 441-443.
  • 38
    Li CW, Dinh GK, Chen JD. Preferential physical and functional interaction of pregnane X receptor with the SMRTalpha isoform. Mol Pharmacol 2009; 75: 363-373.
  • 39
    Johnson DR, Li CW, Chen LY, Ghosh JC, Chen JD. Regulation and binding of pregnane X receptor by nuclear receptor corepressor silencing mediator of retinoid and thyroid hormone receptors (SMRT). Mol Pharmacol 2006; 69: 99-108.
  • 40
    Chen JD, Evans RM. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995; 377: 454-457.
  • 41
    Horlein AJ, Naar AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995; 377: 397-404.
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