Advanced search
Publication Cover
Expert Opinion on Drug Metabolism & Toxicology Volume 2, 2006 - Issue 3
Submit an article Journal homepage
126
Views
30
CrossRef citations to date
0
Altmetric
Review

Functional evolution of the pregnane X receptor

Manisha Iyer Postdoctoral associate, University of Pittsburgh, Department of Pathology, Scaife Hall S-730, 3550 Terrace Street, Pittsburgh, PA 15261, USA
,
Erica J Reschly Postdoctoral associate, University of Pittsburgh, Department of Pathology, Scaife Hall S-730, 3550 Terrace Street, Pittsburgh, PA 15261, USA
&
Matthew D Krasowski Assistant professor, University of Pittsburgh, Department of Pathology, Scaife Hall S-730, 3550 Terrace Street, Pittsburgh, PA 15261, USA. [email protected]
Pages 381-397 | Published online: 30 May 2006

Bibliography

  • ZHANG Z, BURCH PE, COONEY AJ etal.: Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome. Genome Res. (2004) 14(4):580-590.
  • ROBINSON-RECHAVI M, CARPENTIER A-S, DUFFRAISSE M, LAUDET V: How many nuclear hormone receptors are there in the human genome? Trends Genet. (2001) 17(10):554-556.
  • JAILLON O, AURY J-M, BRUNET F etal.: Genome duplication in the telost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature (2004) 431(7011):946-956.
  • ROBINSON-RECHAVI M, BOUSSAU B, LAUDET V: Phylogenetic dating and characterization of gene duplications in vertebrates: the cartilaginous fish reference. Mol. Biol. Evol. (2004) 21(3):580-586.
  • ESCRIVA H, MANZON L, YOUSON J, LAUDET V: Analysis of lamprey and hagfish genes reveals a complex history of gene duplications during early vertebrate evolution. Mol. Biol. Evol. (2002) 19(9):1440-1450.
  • MAGLICH JM, CARAVELLA JA, LAMBERT MH, WILLSON TM, MOORE JT, RAMAMURTHY L: The first completed genome sequence from a teleost fish (Fugu rubripes) adds significant diversity to the nuclear receptor superfamily. Nucleic Acids Res. (2003) 31(14):4051-4058.
  • BLUMBERG B, SABBAGH W, JUGUILON H etal.: SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev. (1998) 12(20):3195-3205.
  • KLIEWER SA, MOORE JT, WADE L etal.: An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell (1998) 92(1):73-82.
  • LEHMANN JM, MCKEE DD, WATSONMA, WILLSON TM, MOOREJT, KLIEWER SA: The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. (1998) 102(5):1016-1023.
  • MOORE LB, MAGLICH JM, MCKEEDD etal.: Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors. Mol. Endocrinol. (2002) 16(5):977-986.
  • MOORE LB, PARKS DJ, JONES SA etal.: Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J. Biol. Chem. (2000) 275(20):15122-15127.
  • KOMOROSKI BJ, ZHANG S, CAI H etal.: Induction and inhibition of cytochromes P450 by the St. Johns wort constituent hyperforin in human hepatocyte cultures. Drug Metab. Dispos. (2004) 32(5):512-518.
  • BERTILSSON G, HEIDRICH J, SVENSSON K etal.: Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc. Nat. Acad. Sci. USA (1998) 95(21):12208-12213.
  • SYNOLD TW, DUSSAULT I, FORMANBM: The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat. Med. (2001) 7(5):584-590.
  • RIPP SL, FITZPATRICK JL, PETERS JM, PROUGH RA: Induction of CYP3A expression by dehydroepiandrosterone: involvement of the pregnane X receptor. Drug Metab. Dispos. (2002) 30(5):570-575.
  • JONES SA, MOORE LB, SHENK JL etal.: The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol. Endocrinol. (2000) 14(1):27-39.
  • HUSTERT E, ZIBAT A, PRESECAN-SIEDEL E etal.: Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab. Dispos. (2001) 29(11):1454-1459.
  • SAVAS U, WESTER MR, GRIFFIN KJ, JOHNSON EF: Rabbit pregnane X receptor is activated by rifampicin. Drug Metab. Dispos. (2000) 28(5):529-537.
  • WENTWORTH JM, AGOSTINI M, LOVE J, SCHWABE JW, CHATTERJEEVKK: St Johns wort, a herbal antidepressant, activates the steroid X receptor. J. Endocrinol. (2000) 166(3):R11-R16.
  • BLUMBERG B, KANG H, BOLADO J etal.: BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites. Genes Dev. (1998) 12(9):1269-1277.
  • HARTLEY DP, DAI X, HE YD etal.: Activators of the rat pregnane X receptor differentially modulate hepatic and intestinal gene expression. Mol. Pharmacol. (2004) 65(5):1159-1171.
  • ZHANG H, LECULYSE E, LIU L etal.: Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation. Arch. Biochem. Biophys. (1999) 368(1):14-22.
  • DROCOURT L, PASCUSSI J-M, ASSENAT E, FABRE J-M, MAUREL P, VILAREM M-J: Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab. Dispos. (2001) 29(10):1325-1331.
  • GERBAL-CHALOIN S, PASCUSSI J-M, PICHARD-GARCIA L etal.: Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab. Dispos. (2001) 29(3):242-251.
  • MAGLICH JM, STOLTZ CM, GOODWIN B, HAWKINS-BROWN D, MOORE JT, KLIEWER SA: Nuclear pregnane X receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic distribution. Mol. Pharmacol. (2002) 62(3):638-646.
  • XIE W, YEUH M-F, RADOMINSKA-PANDYA A etal.: Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor. Proc. Nat. Acad. Sci. USA (2003) 100(7):4150-4155.
  • HO RH, KIM RB: Transporters and drug therapy: implications for drug disposition and disease. Clin. Pharmacol. Ther. (2005) 78(3):260-277.
  • BURK O, ARNOLD KA, NUSSLER AK etal.: Antimalarial artemisin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol. Pharmacol. (2005) 67(6):1954-1965.
  • GEICK A, EICHELBAUM M, BURK O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J. Biol. Chem. (2001) 276(18):14581-14587.
  • PASCUSSI JM, GERBAL-CHALOIN S, DROCOURT L, MAUREL P, VILAREMMJ: The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim. Biophys. Acta (2003) 1619(3):243-253.
  • RESCHLY EJ, KRASOWSKI MD: Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds. Curr. Drug Metab. (2006) (In Press).
  • KLIEWER SA, GOODWIN B, WILLSON TM: The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocrine Rev. (2002) 23(5):687-702.
  • KLIEWER SA: The nuclear pregnane X receptor regulates xenobiotic detoxification. J. Nutrit. (2003) 133(7Suppl.):2444S-2447S.
  • SONODA J, ROSENFELD JM, XU L, EVANS RM, XIE W: A nuclear receptor-mediated xenobiotic response and its implication in drug metabolism and host protection. Curr. Drug Metab. (2003) 4(1):59-72.
  • SONODA J, XIE W, ROSENFELD JM, BARWICK JL, GUZELIAN PS, EVANSRM: Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR). Proc. Nat. Acad. Sci. USA (2002) 99(21):13801-13806.
  • DUSSAULT I, FORMAN BM: The nuclear receptor PXR: a master regulator of homeland defense. Crit. Rev. Eukaryotic Gene Express. (2002) 12(1):53-64.
  • VAN BUREN D, WIDEMAN CA, RIEDM etal.: The antagonistic effect of rifampin upon cyclosporine bioavailability. Transplant. Proc. (1984) 16(6):1642-1645.
  • SCHWARZ UI, BSCHEL B, KIRCH W: Unwanted pregnancy on self-medication with St Johns wort despite hormonal contraception. Br. J. Clin. Pharmacol. (2003) 55(1):112-113.
  • SKOLNICK JL, STOLER BS, KATZ DB, ANDERSTON WH: Rifampin, oral contraceptives, and pregnancy. JAMA (1976) 236(12):1382.
  • WATKINS RE, DAVIS-SEARLES PR, LAMBERT MH, REDINBO MR: Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J. Mol. Biol. (2003) 331(4):815-828.
  • WATKINS RE, MAGLICH JM, MOORELB etal.: 2.1 crystal structure of human PXR in complex with the St. Johns wort compound hyperperforin. Biochemistry (2003) 42(6):1430-1438.
  • WATKINS RE, NOBLE SM, REDINBOMR: Structural insights in the promiscuity and function of the human pregnane X receptor. Curr. Opin. Drug Discov. Devel. (2002) 5(1):150-158.
  • WATKINS RE, WISELY GB, MOORE LB etal.: The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science (2001) 292(5525):2329-2333.
  • CHRENCIK JE, ORANS J, MOORE LB etal.: Structural disorder in the complex of human PXR and the macrolide antibiotic rifampicin. Mol. Endocrinol. (2005) 19(5):1125-1134.
  • ORANS J, TEOTICO DG, REDINBOMR: The nuclear xenobiotic receptor PXR: recent insights and new challenges. Mol. Endocrinol. (2005) 19(12):2891-2900.
  • INGRAHAM HA, REDINBO MR: Orphan nuclear receptors adopted by crystallography. Curr. Opin. Struct. Biol. (2005) 15(6):708-715.
  • CARNAHAN VE, REDINBO MR: Structure and function of the human nuclear xenobiotic receptor PXR. Curr. Drug Metab. (2005) 6(4):357-367.
  • EKINS S, BRAVI G, WIKEL JH, WRIGHTON SA: Three-dimensional quantitativestructure activity relationship analysis of cytochrome P450 3A4 substrates. J. Pharmacol. Exp. Ther. (1999) 291(1):424-433.
  • LI AP, KAMINSKI DL, RASMUSSEN A: Substrates of human hepatic cytochrome P450 3A4. Toxicology (1995) 104(1-3):1-8.
  • LUO G, GUENTHNER T, GAN L-S, HUMPHREYS WG: CYP3A4 induction by xenobiotics: biochemistry, experimental methods and impact on drug discovery and development. Curr. Drug Metab. (2004) 5(6):483-505.
  • QUATTROCHI LC, GUZELIAN PS: CYP3A regulation: from pharmacology to nuclear receptors. Drug Metab. Dispos. (2001) 29(5):615-622.
  • WRIGHTON SA, SCHUETZ EG, THUMMEL KE, SHEN DD, KORZEKWA KR, WATKINS PB: The human CYP3A subfamily: practical considerations. Drug Metab. Rev. (2000) 32(3-4):339-361.
  • EKINS S, KIM RB, LEAKE BF etal.: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol. Pharmacol. (2002) 61(5):964-973.
  • HIGGINS CF: The multidrug resistance P-glycoprotein. Curr. Opin. Cell Biol. (1993) 5(4):684-687.
  • WACHER VJ, WU CY, BENET LZ: Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implication for drug delivery and activity in cancer chemotherapy. Mol. Carcinogenesis (1995) 13(3):129-134.
  • YU DK: The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions. J. Clin. Pharmacol. (1999) 39(12):1203-1211.
  • GOODWIN B, GAUTHIER KC, UMETANI M etal.: Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc. Nat. Acad. Sci. USA (2003) 100(1):223-228.
  • HANDSCHIN C, PODVINEC M, MEYER UA: CXR, a chicken xenobiotic-sensing orphan nuclear receptor, is related to both mammalian pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Proc. Nat. Acad. Sci. USA (2000) 97(20):10769-10774.
  • HANDSCHIN C, PODVINEC M, AMHERD R, LOOSER R, OURLIN J-C, MEYER UA: Cholesterol and bile acids regulate xenosensor signaling in drug-mediated induction of cytochromes P450. J. Biol. Chem. (2002) 277(33):29561-29567.
  • MOORE LB, GOODWIN B, JONES SA etal.: St. Johns wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Nat. Acad. Sci. USA (2000) 97(13):7500-7502.
  • ZHANG W, PURCHIO A, CHEN K, BURNS SM, CONTAG CH, CONTAGPR: Invivo activation of the human CYP3A4 promoter in mouse liver and regulation by pregnane X receptors. Biochem. Pharmacol. (2003) 65(11):1889-1896.
  • MATHENY CJ, ALI RY, YANG X, POLLACK GM: Effect of prototypical inducing agents on P-glycoprotein and CYP3A expression in mouse tissues. Drug Metab. Dispos. (2004) 32(9):1008-1014.
  • GRN F, VENKATESAN RN, TABBMM etal.: Benzoate X receptors and are pharmacologically distinct and do not function as xenobiotic receptors. J. Biol. Chem. (2002) 277(46):43691-43697.
  • HEATH LA, JONES EA, OLD RW: Expression pattern of BXR suggests a role for benzoate ligand-mediated signalling in hatching gland function. Int. J. Dev. Biol. (2000) 44(1):141-144.
  • NISHIKAWA J, SAITO K, SASAKI M, TOMIGAHARA Y, NISHIHARA T: Molecular cloning and functional characterization of a novel nuclear receptor similar to an embryonic benzoate receptor BXR. Biochem. Biophys. Res. Comm. (2000) 277(1):209-215.
  • KRASOWSKI MD, YASUDA K, HAGEYLR, SCHUETZ EG: Evolution of the pregnane X receptor: adaptation to cross-species differences in biliary bile salts. Mol. Endocrinol. (2005) 19(7):1720-1739.
  • KRASOWSKI MD, YASUDA K, HAGEYLR, SCHUETZ EG: Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors). Nucl. Rec. (2005) 3(1):2.
  • CLARK AG, GLANOWSKI S, NIELSENR etal.: Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios. Science (2003) 302(5652):1960-1963.
  • THOMPSON EE, KUTTAB-BOULOS H, KRASOWSKIMD, DI RIENZO A: Functional constraints in the constitutive androstane receptor inferred from human sequence variation and cross-species comparisons. Hum. Genomics (2005) 2(3):168-178.
  • YANG Z, BIELAWSKI JP: Statistical methods for detecting molecular adaptation. Trends Ecol. Evol. (2000) 15(12):496-503.
  • PAGANI F, RAPONI M, BARALLE FE: Synonymous mutations in CFTR exon 12 affect splicing and are not neutral in evolution. Proc. Nat. Acad. Sci. USA (2005) 102(18):6368-6372.
  • ENDO T, IKEO K, GOJOBORI T: Large-scale search for genes on which positive selection may operate. Mol. Biol. Evol. (1996) 13(5):685-690.
  • YANG Z: Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol. Biol. Evol. (1998) 15(5):568-573.
  • YANG Z: Maximum likelihood estimation of large phylogenies and analysis of adaptive evolution in human influenza virus A. J. Mol. Evol. (2000) 51(5):423-432.
  • NIELSEN R, YANG Z: Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics (1998) 148(3):929-936.
  • SCHUETZ EG, STROM S, YASUDA K etal.: Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J. Biol. Chem. (2001) 276(42):39411-39418.
  • XIE W, BARWICK JL, SIMON CM etal.: Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev. (2000) 14(23):3014-3023.
  • LAMBA J, LAMBA V, SCHUETZ E: Genetic variants of PXR (NR1I2) and CAR (NR1I3) and their implications in drug metabolism and pharmacogenetics. Curr. Drug Metab. (2005) 6(4):369-383.
  • ZHANG J, KUEHL P, GREEN ED etal.: The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics (2001) 11(7):555-572.
  • KOYANO S, KUROSE K, OZAWA S etal.: Eleven novel single nucleotide polymorphisms in the NR1I2 (PXR) gene, four of which induce non-synonymous amino acid alterations. Drug Metab. Pharmacokinet. (2002) 17(6):561-565.
  • KOYANO S, KUROSE K, SAITO Y etal.: Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab. Dispos. (2004) 32(1):149-154.
  • EBERSBERGER I, METZLER D, SCHWARZ C, PBO S: Genomewide comparison of DNA sequences between humans and chimpanzees. Am. J. Hum. Genet. (2002) 70(6):1490-1497.
  • WEI P, ZHANG J, DOWHAN DH, HANY, MOORE DD: Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response. Pharmacogenomics J. (2002) 2(2):117-126.
  • HOFMANN AF: The continuing importance of bile acids in liver and intestinal disease. Arch. Intern. Med. (1999) 159(22):2647-2658.
  • HOFMANN AF: Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab. Rev. (2004) 36(3-4):703-722.
  • UPPAL H, TOMA D, SAINI SPS, REN S, JONES TJ, XIE W: Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. Hepatology (2005) 41(1):168-176.
  • ZHANG J, HUANG W, QATANANI M, EVANS RM, MOORE DD: The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J. Biol. Chem. (2004) 279(47):49517-49522.
  • STAUDINGER JL, GOODWIN B, JONES SA etal.: The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Nat. Acad. Sci. USA (2001) 98(6):3369-3374.
  • XIE W, RADOMINSKA-PANDYA A, SHI Y etal.: An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Nat. Acad. Sci. USA (2001) 98(6):3375-3380.
  • MAKISHIMA M, LU TT, XIE W etal.: Vitamin D receptor as an intestinal bile acid sensor. Science (2002) 296(5571):1313-1316.
  • FISCHER S, BEUERS U, SPENGLER U, ZWIEBEL FM, KOEBE H-G: Hepatic levels of bile acids in end-stage chronic cholestatic liver disease. Clin. Chim. Acta (1996) 251(2):173-186.
  • STEDMAN C, ROBERTSON G, COULTER S, LIDDLE C: Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice. J. Biol. Chem. (2004) 279(12):11336-11343.
  • CALI JJ, HSIEH C-L, FRANCKE U, RUSSELL DW: Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J. Biol. Chem. (1991) 266(12):7779-7783.
  • HONDA A, SALEN G, MATSUZAKI Y etal.: Side chain hydroxylations in bile acid biosynthesis catalyzed by CYP3A are markedly up-regulated in Cyp27-/- mice but not in cerebrotendinous xanthomatosis. J. Biol. Chem. (2001) 276(37):34579-34585.
  • HONDA A, SALEN G, MATSUZAKI Y etal.: Differences in hepatic levels of intermediates in bile acid biosynthesis between Cyp27(-/-) mice and CTX. J. Lipid Res. (2001) 42(2):291-300.
  • DUSSAULT I, YOO H-D, LIN M etal.: Identification of an endogenous ligand that activates pregnane X receptor-mediated sterol clearance. Proc. Nat. Acad. Sci. USA (2003) 100(3):833-838.
  • HOFMANN AF, SCHTEINGART CD, HAGEY LR: Species differences in bile acid metabolism. In: International Falk Symposium: Bile acids in liver diseases. G Paumgartner, U Beuers (Eds), Kluwer Academic Publishers, Dordrecht, The Netherlands (1995):3-30.
  • HAGEY LR: Bile acid biodiversity in vertebrates: chemistry and evolutionary implications. UMI, Ann Arbor, MI, USA (1992).
  • UNE M, HOSHITA T: Natural occurrence and chemical synthesis of bile alcohols, higher bile acids, and short side chain bile acids. Hiroshima J. Med. Sci. (1994) 43(2):37-67.
  • MOSCHETTA A, XU F, HAGEY LR etal.: A phylogenetic survey of biliary lipids in vertebrates. J. Lipid Res. (2005) 46(10):2221-2232.
  • ANDERSON IG, BRIGGS T, HASLEWOOD GAD: Comparative studies of bile salts. 18. The chemistry of cyprinol. Biochem. J. (1964) 90(2):303-308.
  • GOTO T, HOLZINGER F, HAGEY LR etal.: Physicochemical and physiological properties of 5-cyprinol sulfate, the toxic bile salt of cyprinid fish. J. Lipid Res. (2003) 44(9):1643-1651.
  • HASLEWOOD GAD, TKS L: Comparative studies of bile salts: bile salts of the lamprey Petromyzon marinus L. Biochem. J. (1969) 114(2):179-184.
  • HASLEWOOD GAD: Comparative studies of bile salts. Myxinol disulphate, the principal bile salt of hagfish (Myxinidae). Biochem. J. (1966) 100(1):233-237.
  • KARPEN SJ: Exercising the nuclear option to treat cholestasis: CAR and PXR ligands. Hepatology (2005) 42(2):266-269.
  • BACHS L, PARES A, ELENA M, PIERAC, RODES J: Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet (1989) 1(8638):574-576.
  • TRACY TS, VENKATARAMANAN R, GLOVER DD, CARITIS SN: Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A4 activity) during pregnancy. Am. J. Obstet. Gynecol. (2005) 192(2):633-639.
  • KASHUBA AD, BERTINO JS, ROCCIML, KULAWY RW, BECK DJ, NAFZIGER AN: Quantification of 3-month intraindividual variability and the influence of sex and menstrual cycle phase on CYP3A activity as measured by phenotyping with intravenous midazolam. Clin. Pharmacol. Ther. (1998) 64(3):269-277.
  • KHARASCH ED, MAUTZ D, SENN T, LEUTZ G, COX K: Menstrual cycle variability in midazolam pharmacokinetics. J. Clin. Pharmacol. (1999) 39(3):275-280.
  • KHARASCH ED, RUSSELL M, GARTON K, LENTZ G, BOWDLE TA, COX K: Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe. Anesthesiology (1997) 87(1):26-35.
  • MITCHELL BF, MITCHELL JM, CHOWDHURY J etal.: Metabolites of progesterone and the pregnane X receptor: a novel pathway regulating uterine contractility in pregnancy? Am. J. Obstet. Gynecol. (2005) 192(4):1304-1312.
  • FORMAN BM, TZAMELI I, CHOI H-S etal.: Androstane metabolites bind to and deactivate the nuclear receptor CAR-. Nature (1998) 395(6702):612-615.
  • SINGER AG: A chemistry of mammalian pheromones. J. Steroid Biochem. Mol. Biol. (1991) 39(4B):627-632.
  • CLAUS R, ALSING W: Occurence of 5-androst-16-en-3-one, a boar pheromone, in man and its relationship to testosterone. J. Endocrinol. (1976) 68(3):483-484.
  • XU H, RAJESAN R, HARPER P etal.: Induction of cytochrome P450 1A by cow milk-based formula: a comparative study between human milk and formula. Br. J. Pharmacol. (2005) 146(2):296-305.
  • TRABER MG: Vitamin E, nuclear receptors and xenobiotic metabolism. Arch. Biochem. Biophys. (2004) 423(1):6-11.
  • BRIGELIUS-FLOH R: Induction of drug metabolizing enzymes by vitamin E. J. Plant Physiol. (2005) 162(7):797-802.
  • LANDES N, PFLUGER P, KLUTH D etal.: Vitamin E activates gene expression via the pregnane X receptor. Biochem. Pharmacol. (2003) 65(2):269-273.
  • RHL R, SCZECH R, LANDES N, PFLUGER P, KLUTH D, SCHWEIGERTFJ: Carotenoids and their metabolites are naturally occurring activators of gene expression via the pregnane X receptor. Eur. J. Nutrit. (2004) 43(6):336-343.
  • HAHN ME: Aryl hydrocarbon receptors: diversity and evolution. Chem. Biol. Interact. (2002) 141(1-2):131-160.
  • SCHUETZ EG, SCHUETZ JD, GROGAN WM etal.: Expression of cytochrome P450 3A in amphibian, rat, and human kidney. Arch. Biochem. Biophys. (1992) 294(1):206-214.
  • ERTL RP, STEGEMAN JJ, WINSTONGW: Induction time course of cytochromes P450 by phenobarbital and 3-methylcholanthrene by pretreatment in liver microsomes of Alligator mississippiensis. Biochem. Pharmacol. (1998) 55(9):1513-1521.
  • HASSELBERG L, MEIER S, SVARDAL A, HEGELUND T, CELANDER MC: Effects of alkylphenols on CYP1A and CYP3A expression in first spawning Atlantic cod (Gadus morhua). Aquat. Toxicol. (2004) 67(4):303-313.
  • HEGELUND T, OTTOSSON K, RDINGER M, TOMBERG P, CELANDER MC: Effects of the antifungal imidazole ketoconazole on CYP1A and CYP3A in rainbow trout and killifish. Environ. Toxicol. Chem. (2004) 23(5):1326-1334.
  • BRESOLIN T, DE FREITAS REBELO M, BAINY ACD: Expression of PXR, CYP3A, and MDR1 genes in liver of zebrafish. Comp. Biochem. Physiol. Part C (2005) 140(3-4):403-407.
  • TSENG H-P, HSEU T-H, BUHLER DR, WANG W-D, HU C-H: Constitutive and xenobiotics-induced expression of a novel CYP3A gene from zebrafish larva. Toxicol. Appl. Pharmacol. (2005) 205(3):247-258.
  • DEHAL P, SATOU Y, CAMPBELL RK etal.: The draft genome of Ciona intestinalis: insights into vertebrate origins. Science (2002) 298(5601):2157-2167.
  • HANDSCHIN C, BLAETTLER S, ROTH A etal.: The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals. Nucl. Rec. (2004) 2(1):7.
  • APARICIO S, CHAPMAN J, STUPK E etal.: Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes. Science (2002) 297(5585):1301-1310.
  • HILLIER LW, MILLER W, BIRNEY E etal.: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature (2004) 432(7018):695-716.
  • XIE W, BARWICK JL, DOWNES M etal.: Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature (2000) 406(6794):435-439.
  • SHAPIRO LE, SHEAR NH: Drug interactions: proteins, pumps, and P450s. J. Am. Acad. Dermatol. (2002) 47(4):467-484.
  • MICHALETS EL: Update: clinical significant cytochrome P450 drug interactions. Pharmacotherapy (1998) 18(1):84-112.
  • DICKINS M: Induction of cytochromes P450. Curr. Top. Med. Chem. (2004) 4(16):1745-1766.
  • SCHUETZ EG: Induction of cytochromes P450. Curr. Drug Metab. (2001) 2(2):139-147.
  • YUEH M-F, KAWAHARA M, RAUCY J: High volume bioassays to assess CYP3A4-mediated drug interactions: induction and inhibition in a single cell line. Drug Metab. Dispos. (2005) 33(1):38-48.
  • VERMEIR M, ANNAERT P, MAMIDIRNVS, ROYMANS D, MEULDERMANS W, MANNENS G: Cell-based models to study hepatic drug metabolism and enzyme induction in humans. Expert Opin. Drug Metab. Toxicol. (2006) 1(1):75-90.
  • MOORE JT, KLIEWER SA: Use of the nuclear receptor PXR to predict drug interactions. Toxicology (2000) 153(1-3):1-10.
  • GMEZ-LECHN MJ, DONATO MT, CASTELL JV, JOVER R: Human hepatocytes as a tool for studying toxicity and drug metabolism. Curr. Drug Metab. (2003) 5(5):292-312.
  • LECLUYSE EL, ALEXANDRE E, HAMILTON GA etal.: Isolation and culture of primary human hepatocytes. Methods Mol. Biol. (2005) 290(1):207-229.
  • ZHU Z, KIM S, CHEN TC etal.: Correlation of high-throughput pregnane X receptor (PXR) transactivation and binding assays. J. Biomol. Screening (2004) 9(6):533-540.
  • VIGNATI LA, BOGNI A, GROSSI P, MONSHOUWER M: A human and mouse pregnane X receptor reporter gene assay in combination with cytotoxicity measurements as a tool to evaluate species-specific CYP3A induction. Toxicology (2004) 199:23-33.
  • DAI G, WAN YJ: Animal models of xenobiotic receptors. Curr. Drug Metab. (2005) 6(4):341-355.
  • NALLANI SC, GOODWIN B, MAGLICH JM, BUCKLEY DJ, BUCKLEY AR, DESAI PB: Induction of cytochrome P450 3A by paclitaxel in mice: pivotal role of the nuclear xenobiotic receptor, pregnane X receptor. Drug Metab. Dispos. (2003) 31(5):681-684.
  • ANAKK S, KALSOTRA A, KIKUTA Y etal.: CAR/PXR provide directives for Cyp3a41 gene regulation differently from Cyp3a11. Pharmacogenomics J. (2004) 4(2):91-101.
  • STAUDINGER J, LIU Y, MADA A, HABEEBU S, KLAASSEN CD: Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Drug Metab. Dispos. (2001) 29(11):1467-1472.
  • SONODA J, CHONG LW, DOWNES M etal.: Pregnane X receptor prevents hepatorenal toxicity from cholesterol metabolites. Proc. Nat. Acad. Sci. USA (2005) 102(6):2198-2203.
  • TABB MM, SUN A, ZHOU C etal.: Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic SXR. J. Biol. Chem. (2003) 278(45):43919-43927.
  • XIE W, EVANS RM: Pharmaceutical use of mouse models humanized for the xenobiotic receptor. Drug Discov. Today (2002) 7(9):509-515.
  • KEMP CA, MARCHAL J-D, SUTCLIFFE MJ: Progress in cytochrome P450 active site modeling. Arch. Biochem. Biophys. (2005) 433(2):361-368.
  • PAJEVA IK, WIESE M: Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J. Med. Chem. (2002) 45(26):5671-5684.
  • GOMBAR VK, POLLI JW, HUMPHREYS JE, WRING SA, SERABJIT CS: Predicting P-glycoprotein substrates by a quantitative structure-activity relationship model. J. Pharm. Sci. (2004) 93(4):957-968.
  • EKINS S, KIM RB, LEAKE BF etal.: Application of three-dimensional quantitative structureactivity relationships of P-glycoprotein inhibitors and substrates. Mol. Pharmacol. (2002) 61(5):974-981.
  • EKINS S, MIRNY L, SCHUETZ EG: A ligand-based approach to understanding selectivity of nuclear hormone receptors PXR, CAR, FXR, LXR and LXR. Pharm. Res. (2002) 19(12):1788-1800.
  • EKINS S, WRIGHTON SA: Application of in silico approaches to predicting drug-drug metabolism. J. Pharmacol. Toxicol. Methods (2001) 45(1):65-69.
  • KOBAYASHI K, YAMAGAMI Y, HIGUCHI T, HOSOKAWA M, CHIBAK: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab. Dispos. (2004) 32(4):468-472.
  • EKINS S, ERICKSON JA: A pharmacophore for human pregnane X receptor ligands. Drug Metab. Dispos. (2002) 30(1):96-99.
  • SCHUSTER D, LANGER T: The identification of ligand features essential for PXR activation. J. Med. Chem. (2005) 45(2):431-439.
  • TIRONA RG, LEAKE BF, PODUST LM, KIM RB: Identification of amino acids in rat pregnane X receptor that determine species-specific activation. Mol. Pharmacol. (2004) 65(1):36-44.
  • ROCHEL N, WURTZ JM, MITSCHLERA, KLAHOLZ B, MORASD: The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell (2000) 5(1):173-179.
  • TOCCHINI-VALENTINI G, ROCHELN, WURTZ JM, MITSCHLERA, MORAS D: Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. Proc. Nat. Acad. Sci. USA (2001) 98(10):5491-5496.
  • TOCCHINI-VALENTINI G, ROCHELN, WURTZ J-M, MORAS D: Crystal structure of the vitamin D receptor liganded with the vitamin D side chain analogues calicotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by a further side chain modification. J. Med. Chem. (2004) 47(8):1956-1961.
  • MIZWICKI MT, KEIDEL D, BULA CM etal.: Identification of an alternative ligand-binding pocket in the nuclear vitamin D receptor and its functional importance in 1,25(OH)2-vitamin D3 signaling. Proc. Nat. Acad. Sci. USA (2004) 101(35):12876-12881.
  • XU RX, LAMBERT MH, WISELY BB etal.: A structural basis for constitutive activity in the human CAR/RXR heterodimer. Mol. Cell (2004) 16(6):919-928.
  • SUINO K, PENG L, REYNOLDS R etal.: The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization. Mol. Cell (2004) 16(6):893-905.
  • SHAN L, VINCENT J, BRUNZELLE JS etal.: Structure of the murine constitutive androstane receptor complexed to androstenol: a molecular basis for inverse agonism. Mol. Cell (2004) 16(6):907-917.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.