The nuclear pregnane X receptor: A key regulator of xenobiotic metabolism

Endocrine Reviews

Volumn 23, Issue 5, 2002, Pages 687-702

  Kliewer, Steven A ^a,b   Goodwin, Bryan ^a   Willson, Timothy M ^a  

^a GLAXOSMITHKLINE   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

16ALPHA CYANOPREGNENOLONE; 4 HYDROXYTAMOXIFEN; ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; BILE ACID; CLOTRIMAZOLE; CYPROTERONE ACETATE; CYTOCHROME P450 3A; DEXAMETHASONE; GLUTETHIMIDE; HYPERFORIN; HYPERICUM PERFORATUM EXTRACT; LITHOCHOLIC ACID; METYRAPONE; MEVINOLIN; MIFEPRISTONE; NIFEDIPINE; PACLITAXEL; PHENOBARBITAL; PREGNANE X RECEPTOR; PREGNANEDIONE; RETINOIC ACID RECEPTOR; RIFAMPICIN; RITONAVIR; SPIRONOLACTONE; STEROID; TAMOXIFEN; TRABECTEDIN; TROGLITAZONE; XENOBIOTIC AGENT;

ARTICLE; BILE ACID METABOLISM; DNA BINDING; DNA RESPONSIVE ELEMENT; ENZYME INDUCTION; GENE EXPRESSION; HUMAN; HYDROPHOBICITY; LIGAND BINDING; MOLECULAR CLONING; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN POLYMORPHISM; PROTEIN STRUCTURE; RECEPTOR BINDING; RECEPTOR UPREGULATION; XENOBIOTIC METABOLISM;

AMINO ACID SEQUENCE; ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BILE ACIDS AND SALTS; BINDING SITES; CELL NUCLEUS; CLONING, MOLECULAR; CYTOCHROME P-450 CYP3A; DIMERIZATION; DNA; GENE EXPRESSION REGULATION; HUMANS; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; OXIDOREDUCTASES, N-DEMETHYLATING; POLYMORPHISM, GENETIC; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, RETINOIC ACID; RECEPTORS, STEROID; RESPONSE ELEMENTS; RETINOID X RECEPTORS; TRANSCRIPTION FACTORS; XENOBIOTICS;

EID: 0036799870     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2001-0038     Document Type: Article

References (155)

1. Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, Gunsalus IC, Nebert DW 1996 P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 6:1-42
2. Denison MS, Whitlock Jr JP 1995 Xenobiotic-inducible transcription of cytochrome P450 genes. J Biol Chem 270:18175-18178
3. Maurel P 1996 The CYP3A family. In: Ioannides C, ed. Cytochromes P450: metabolic and toxicological aspects. Boca Raton, FL: CRC Press, Inc.; pp 241-270
4. Wrighton SA, Schuetz EG, Thummel KE, Shen DD, Korzekwa KR, Watkins PB 2000 The human CYP3A subfamily: practical considerations. Drug Metab Rev 32:339-361
5. Li AP, Kaminski DL, Rasmussen A 1995 Substrates of human hepatic cytochrome P450 3A4. Toxicology 104:1-8
6. Guengerich FP 1999 Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol 39:1-17
7. Selye H 1971 Hormones and resistance. J Pharm Sci 60:1-28
8. Michalets EL 1998 Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 18:84-112
9. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterstrom RH, Perlmann T, Lehmann JM 1998 An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92:73-82
10. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA 1998 The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 102:1016-1023
11. Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Backman M, Ohlsson R, Postlind H, Blomquist P, Berkenstam A 1998 Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 95:12208-12213
12. Blumberg B, Sabbagh Jr W, Juguilon H, Bolado Jr J, van Meter CM, Ong ES, Evans RM 1998 SXR, a novel steroid and xenobioticsensing nuclear receptor. Genes Dev 12:3195-3205
13. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P 1995 The nuclear receptor superfamily: the second decade. Cell 83:835-839
14. Giguere V 1999 Orphan nuclear receptors: from gene to function. Endocr Rev 20:689-725
15. Xie W, Barwick JL, Downes M, Blumberg B, Simon CM, Nelson MC, Neuschwander-Tetri BA, Brunt EM, Guzelian PS, Evans RM 2000 Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 406:435-439
16. Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, Willson TM, Koller BH, Kliewer SA 2001 The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 98:3369-3374
17. Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, Redinbo MR 2001 The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 292:2329-2333
18. Lu AY, Somogyi A, West S, Kuntzman R, Conney AH 1972 Pregnenolone-16α-carbonitrile: a new type of inducer of drug-metabolizing enzymes. Arch Biochem Biophys 152:457-462
19. Elshourbagy NA, Guzelian PS 1980 Separation, purification, and characterization of a novel form of hepatic cytochrome P-450 from rats treated with pregnenolone-16α-carbonitrile. J Biol Chem 255:1279-1285
20. Hardwick JP, Gonzalez FJ, Kasper CB 1983 Cloning of DNA complementary to cytochrome P-450 induced by pregnenolone-16α-carbonitrile. Characterization of its mRNA, gene, and induction response. J Biol Chem 258:10182-10186
21. Gonzalez FJ, Nebert DW, Hardwick JP, Kasper CB 1985 Complete cDNA and protein sequence of a pregnenolone 16α-carbonitrile-induced cytochrome P-450. A representative of a new gene family. J Biol Chem 260:7435-7441
22. Heuman DM, Gallagher EJ, Barwick JL, Elshourbagy NA, Guzelian PS 1982 Immunochemical evidence for induction of a common form of hepatic cytochrome P-450 in rats treated with pregnenolone-16α-carbonitrile or other steroidal or non-steroidal agents. Mol Pharmacol 21:753-760
23. Schuetz EG, Wrighton SA, Barwick JL, Guzelian PS 1984 Induction of cytochrome P-450 by glucocorticoids in rat liver. I. Evidence that glucocorticoids and pregnenolone 16α-carbonitrile regulate de novo synthesis of a common form of cytochrome P-450 in cultures of adult rat hepatocytes and in the liver in vivo. J Biol Chem 259:1999-2006
24. Schuetz EG, Guzelian PS 1984 Induction of cytochrome P-450 by glucocorticoids in rat liver. II. Evidence that glucocorticoids regulate induction of cytochrome P-450 by a nonclassical receptor mechanism. J Biol Chem 259:2007-2012
25. Burger HJ, Schuetz JD, Schuetz EG, Guzelian PS 1992 Paradoxical transcriptional activation of rat liver cytochrome P-450 3A1 by dexamethasone and the antiglucocorticoid pregnenolone 16α-carbonitrile: analysis by transient transfection into primary monolayer cultures of adult rat hepatocytes. Proc Natl Acad Sci USA 89:2145-2149
26. Schuetz EG, Wrighton SA, Sale SH, Guzelian PS 1986 Regulation of cytochrome P-450p by phenobarbital and phenobarbital-like inducers in adult rat hepatocytes in primary monolayer culture and in vivo. Biochemistry 25:1124-1133
27. Wrighton SA, Schuetz EG, Watkins PB, Maurel P, Barwick J, Bailey BS, Hartle HT, Young B, Guzelian P 1985 Demonstration in multiple species of inducible hepatic cytochromes P-450 and their mRNAs related to the glucocorticoid-inducible cytochrome P-450 of the rat. Mol Pharmacol 28:312-321
28. Goodwin B, Liddle C, Murray M, Tapner M, Rooney T, Farrell GC 1996 Effects of metyrapone on expression of CYPs 2C11, 3A2, and other 3A genes in rat hepatocytes cultured on matrigel. Biochem Pharmacol 52:219-227
29. Wright MC, Paine AJ, Skett P, Auld R 1994 Induction of rat hepatic glucocorticoid-inducible cytochrome P450 3A by metyrapone. J Steroid Biochem Mol Biol 48:271-276
30. Zangar RC, Okita JR, Kim H, Thomas PE, Anderson A, Edwards RJ, Springer DL, Okita RT 1999 Effect of calcium channel antagonists nifedipine and nicardipine on rat cytochrome P-450 2B and 3A forms. J Pharmacol Exp Ther 290:1436-1441
31. Rodrigues AD, Waddell PR, Ah-Sing E, Morris BA, Wolf CR, Ioannides C 1988 Induction of the rat hepatic microsomal mixed-function oxidases by 3 imidazole-containing antifungal agents: selectivity for the cytochrome P-450IIB and P-450III families of cytochromes P-450. Toxicology 50:283-301
32. Hostetler KA, Wrighton SA, Molowa DT, Thomas PE, Levin W, Guzelian PS 1989 Coinduction of multiple hepatic cytochrome P-450 proteins and their mRNAs in rats treated with imidazole antimycotic agents. Mol Pharmacol 35:279-285
33. Kocarek TA, Schuetz EG, Strom SC, Fisher RA, Guzelian PS 1995 Comparative analysis of cytochrome P4503A induction in primary cultures of rat, rabbit, and human hepatocytes. Drug Metab Dispos 23:415-421
34. Wrighton SA, Maurel P, Schuetz EG, Watkins PB, Young B, Guzelian PS 1985 Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P-450p. Biochemistry 24:2171-2178
35. Singleton DW, Lei XD, Webb SJ, Prough RA, Geoghegan TE 1999 Cytochrome P-450 mRNAs are modulated by dehydroepiandrosterone, nafenopin, and triiodothyronine. Drug Metab Dispos 27:193-200
36. Williams JA, Chenery RJ, Berkhout TA, Hawksworth GM 1997 Induction of cytochrome P4503A by the antiglucocorticoid mifepristone and a novel hypocholesterolaemic drug. Drug Metab Dispos 25:757-761
37. Watkins PB, Wrighton SA, Maurel P, Schuetz EG, Mendez-Picon G, Parker GA, Guzelian PS 1985 Identification of an inducible form of cytochrome P-450 in human liver. Proc Natl Acad Sci USA 82:6310-6314
38. Watkins PB, Murray SA, Winkelman LG, Heuman DM, Wrighton SA, Guzelian PS 1989 Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients. J Clin Invest 83:688-697
39. Pichard L, Fabre I, Fabre G, Domergue J, Saint Aubert B, Mourad G, Maurel P 1990 Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos 18:595-606
40. Ged C, Rouillon JM, Pichard L, Combalbert J, Bressot N, Bories P, Michel H, Beaune P, Maurel P 1989 The increase in urinary excretion of 6 β-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br J Clin Pharmacol 28:373-387
41. LeCluyse EL 2001 Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur J Pharm Sci 13:343-368
42. Strom SC, Pisarov LA, Dorko K, Thompson MT, Schuetz JD, Schuetz EG 1996 Use of human hepatocytes to study P450 gene induction. Methods Enzymol 272:388-401
43. Schuetz EG, Schuetz JD, Strom SC, Thompson MT, Fisher RA, Molowa DT, Li D, Guzelian PS 1993 Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes. Hepatology 18:1254-1262
44. Combalbert J, Fabre I, Fabre G, Dalet I, Derancourt J, Cano JP, Maurel P 1989 Metabolism of cyclosporin A. IV. Purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily. Drug Metab Dispos 17:197-207
45. Pichard L, Fabre I, Daujat M, Domergue J, Joyeux H, Maurel P 1992 Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Mol Pharmacol 41:1047-1055
46. Liddle C, Goodwin BJ, George J, Tapner M, Farrell GC 1998 Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab 83:2411-2416
47. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, Domergue J, Maurel P 1992 Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J 6:752-758
48. Wright MC, Maurel P, Paine AJ 1996 Induction of cytochrome P450 3A by metyrapone in human hepatocyte culture. Hum Exp Toxicol 15:203-204
49. Daujat M, Pichard L, Dalet C, Larroque C, Bonfils C, Pompon D, Li D, Guzelian PS, Maurel P 1987 Expression of five forms of microsomal cytochrome P-450 in primary cultures of rabbit hepatocytes treated with various classes of inducers. Biochem Pharmacol 36:3597-3606
50. Potenza CL, Pendurthi UR, Strom DK, Tukey RH, Griffin KJ, Schwab GE, Johnson EF 1989 Regulation of the rabbit cytochrome P-450 3c gene. Age-dependent expression and transcriptional activation by rifampicin. J Biol Chem 264:16222-16228
51. Huss JM, Wang SI, Astrom A, McQuiddy P, Kasper CB 1996 Dexamethasone responsiveness of a major glucocorticoid-inducible CYP3A gene is mediated by elements unrelated to a glucocorticoid receptor binding motif. Proc Natl Acad Sci USA 93:4666-4670
52. Quattrochi LC, Mills AS, Barwick JL, Yockey CB, Guzelian PS 1995 A novel cis-acting element in a liver cytochrome P450 3A gene confers synergistic induction by glucocorticoids plus antiglucocorticoids. J Biol Chem 270:28917-28923
53. Miyata M, Nagata K, Yamazoe Y, Kato R 1995 Transcriptional elements directing a liver-specific expression of P450/6βA (CYP3A2) gene-encoding testosterone 6β-hydroxylase. Arch Biochem Biophys 318:71-79
54. Huss JM, Kasper CB 1998 Nuclear receptor involvement in the regulation of rat cytochrome P450 3A23 expression. J Biol Chem 273:16155-16162
55. Huss JM, Wang SI, Kasper CB 1999 Differential glucocorticoid responses of CYP3A23 and CYP3A2 are mediated by selective binding of orphan nuclear receptors. Arch Biochem Biophys 372:321-332
56. Glass CK 1994 Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr Rev 15:391-407
57. Ogino M, Nagata K, Miyata M, Yamazoe Y 1999 Hepatocyte nuclear factor 4-mediated activation of rat CYP3A1 gene and its modes of modulation by apolipoprotein AI regulatory protein I and v-ErbA-related protein 3. Arch Biochem Biophys 362:32-37
58. Mangelsdorf DJ, Evans RM 1995 The RXR heterodimers and orphan receptors. Cell 83:841-850
59. Quattrochi LC, Yockey CB, Barwick JL, Guzelian PS 1998 Characterization of DNA-binding proteins required for glucocorticoid induction of CYP3A23. Arch Biochem Biophys 349:251-260
60. Barwick JL, Quattrochi LC, Mills AS, Potenza C, Tukey RH, Guzelian PS 1996 Trans-species gene transfer for analysis of glucocorticoid-inducible transcriptional activation of transiently expressed human CYP3A4 and rabbit CYP3A6 in primary cultures of adult rat and rabbit hepatocytes. Mol Pharmacol 50:10-16
61. Weatherman RV, Fletterick RJ, Scanlan TS 1999 Nuclear-receptor ligands and ligand-binding domains. Annu Rev Biochem 68:559-581
62. 1999 A unified nomenclature system for the nuclear receptor superfamily. Cell 97:161-163
63. Blumberg B, Kang H, Bolado Jr J, Chen H, Craig AG, Moreno TA, Umesono K, Perlmann T, De Robertis EM, Evans RM 1998 BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites. Genes Dev 12:1269-1277
64. Nishikawa J, Saito K, Sasaki M, Tomigahara Y, Nishihara T 2000 Molecular cloning and functional characterization of a novel nuclear receptor similar to an embryonic benzoate receptor BXR. Biochem Biophys Res Commun 277:209-215
65. Moore LB, Maglich JM, McKee DD, Wisely B, Willson TM, Kliewer SA, Lambert MH, Moore JT 2002 Pregnane X receptor (PXR), constitutive androstane receptor (CAR), and benzoate X receptor (BXR) define three pharmacologically distinct classes of nuclear receptors. Mol Endocrinol 16:977-986
66. Handschin C, Podvinec M, Meyer UA 2000 CXR, a chicken xenobiotic-sensing orphan nuclear receptor, is related to both mammalian pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Proc Natl Acad Sci USA 97:10769-10774
67. Jones SA, Moore LB, Shenk JL, Wisely GB, Hamilton GA, McKee DD, Tomkinson NC, LeCluyse EL, Lambert MH, Willson TM, Kliewer SA, Moore JT 2000 The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27-39
68. Savas U, Wester MR, Griffin KJ, Johnson EF 2000 Rabbit pregnane X receptor is activated by rifampicin. Drug Metab Dispos 28:529-537
69. Zhang H, LeCulyse E, Liu L, Hu M, Matoney L, Zhu W, Yan B 1999 Rat pregnane X receptor: molecular cloning, tissue distribution, and xenobiotic regulation. Arch Biochem Biophys 368:14-22
70. Maglich JM, Sluder A, Guan X, Shi Y, McKee DD, Carrick K, Kamdar K, Willson TM, Moore JT 2001 Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes. Genome Biol 2:RESEARCH0029
71. Robinson-Rechavi M, Carpentier A, Duffraisse M, Laudet V 2001 How many nuclear hormone receptors are there in the human genome? Trends Genet 17:554-556
72. Dotzlaw H, Leygue E, Watson P, Murphy LC 1999 The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin Cancer Res 5:2103-2107
73. Hustert E, Zibat A, Presecan-Siedel E, Eiselt R, Mueller R, Fuss C, Brehm I, Brinkmann U, Eichelbaum M, Wojnowski L, Burk O 2001 Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab Dispos 29:1454-1459
74. Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson Jr JR, Schuetz EG, Boguski MS 2001 The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 11:555-572
75. Masuyama H, Hiramatsu Y, Mizutani Y, Inoshita H, Kudo T 2001 The expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in perinatal mouse. Mol Cell Endocrinol 172:47-56
76. Pascussi JM, Drocourt L, Fabre JM, Maurel P, Vilarem MJ 2000 Dexamethasone induces pregnane X receptor and retinoid X receptor-α expression in human hepatocytes: synergistic increase of CYP3A4 induction by pregnane x receptor activators. Mol Pharmacol 58:361-372
77. Huss JM, Kasper CB 2000 Two-stage glucocorticoid induction of CYP3A23 through both the glucocorticoid and pregnane X receptors. Mol Pharmacol 58:48-57
78. Evans RM 1988 The steroid and thyroid hormone receptor superfamily. Science 240:889-895
79. Goodwin B, Hodgson E, Liddle C 1999 The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 56:1329-1339
80. Schuetz EG, Brimer C, Schuetz JD 1998 Environmental xenobiotics and the antihormones cyproterone acetate and spironolactone use the nuclear hormone pregnenolone X receptor to activate the CYP3A23 hormone response element. Mol Pharmacol 54:1113-1117
81. Wright MC 1999 The cytochrome P450 3A4 inducer metyrapone is an activator of the human pregnane X receptor. Biochem Soc Trans 27:387-391
82. Drocourt L, Pascussi JM, Assenat E, Fabre JM, Maurel P, Vilarem MJ 2001 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 29:1325-1331
83. Dussault I, Lin M, Hollister K, Wang EH, Synold TW, Forman BM 2001 Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem 276:33309-33312
84. Synold TW, Dussault I, Forman BM 2001 The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 7:584-590
85. Desai PB, Nallani SC, Sane RS, Moore LB, Goodwin BJ, Buckley DJ, Buckley AR 2002 Induction of cytochrome P450 3A4 in primary human hepatocytes and activation of the human pregnane X receptor by tamoxifen and 4-hydroxytamoxifen. Drug Metab Dispos 30:608-612
86. Handschin C, Podvinec M, Stockli J, Hoffmann K, Meyer UA 2001 Conservation of signaling pathways of xenobiotic-sensing orphan nuclear receptors, chicken xenobiotic receptor, constitutive androstane receptor, and pregnane X receptor, from birds to humans. Mol Endocrinol 15:1571-1585
87. Masuyama H, Hiramatsu Y, Kunitomi M, Kudo T, MacDonald PN 2000 Endocrine disrupting chemicals, phthalic acid and nonylphenol, activate pregnane X receptor-mediated transcription. Mol Endocrinol 14:421-428
88. Takeshita A, Koibuchi N, Oka J, Taguchi M, Shishiba Y, Ozawa Y 2001 Bisphenol-A, an environmental estrogen, activates the human orphan nuclear receptor, steroid and xenobiotic receptor-mediated transcription. Eur J Endocrinol 145:513-517
89. Moore LB, Parks DJ, Jones SA, Bledsoe RK, Consler TG, Stimmel JB, Goodwin B, Liddle C, Blanchard SG, Willson TM; Collins JL, Kliewer SA 2000 Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem 275:15122-15127
90. Krey G, Braissant O, L'Horset F, Kalkhoven E, Perroud M, Parker MG, Wahli W 1997 Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol 11:779-791
91. Pascussi JM, Jounaidi Y, Drocourt L, Domergue J, Balabaud C, Maurel P, Vilarem MJ 1999 Evidence for the presence of a functional pregnane X receptor response element in the CYP3A7 promoter gene. Biochem Biophys Res Commun 260:377-381
92. Xie W, Barwick JL, Simon CM, Pierce AM, Safe S, Blumberg B, Guzelian PS, Evans RM 2000 Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes Dev 14:3014-3023
93. Goodwin B, Moore LB, Stoltz CM, McKee DD, Kliewer SA 2001 Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol Pharmacol 60:427-431
94. Geick A, Eichelbaum M, Burk O 2001 Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581-14587
95. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA 2002 Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor and constitutive androstane receptor. J Biol Chem 277:2908-2915
96. Eichelbaum M, Burk O 2001 CYP3A genetics in drug metabolism. Nat Med 7:285-287
97. Ozdemir V, Kalowa W, Tang BK, Paterson AD, Walker SE, Endrenyi L, Kashuba AD 2000 Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method. Pharmacogenetics 10:373-388
98. Staudinger J, Liu Y, Madan A, Habeebu S, Klaassen CD 2001 Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Drug Metab Dispos 29:1467-1472
99. Maglich JM, Stoltz CM, Goodwin B, Hawkins-Brown D, Moore JT, Kliewer SA 2002 Nuclear receptors PXR and CAR regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62:638-646
100. Gerbal-Chaloin S, Pascussi JM, Pichard-Garcia L, Daujat M, Waechter F, Fabre JM, Carrere N, Maurel P 2001 Induction of CYP2C genes in human hepatocytes in primary culture. Drug Metab Dispos 29:242-251
101. Gerbal-Chaloin S, Daujat M, Pascussi JM, Pichard-Garcia L, Vilarem MJ, Maurel PJ 2002 Transcriptional regulation of CYP2C9 gene. Role of glucocorticoid receptor and constitutive androstane receptor. J Biol Chem 277:209-217
102. Falkner KC, Pinaire JA, Xiao GH, Geoghegan TE, Prough RA 2001 Regulation of the rat glutathione S-transferase A2 gene by glucocorticoids: involvement of both the glucocorticoid and pregnane X receptors. Mol Pharmacol 60:611-619
103. Liu L, Klaassen CD 1996 Regulation of hepatic sulfotransferases by steroidal chemicals in rats. Drug Metab Dispos 24:854-858
104. Dunn Jr RT, Gleason BA, Hartley DP, Klaassen CD 1999 Postnatal ontogeny and hormonal regulation of sulfotransferase SULT1B1 in male and female rats. J Pharmacol Exp Ther 290:319-324
105. Runge-Morris M, Wu W, Kocarek TA 1999 Regulation of rat hepatic hydroxysteroid sulfotransferase (SULT2-40/41) gene expression by glucocorticoids: evidence for a dual mechanism of transcriptional control. Mol Pharmacol 56:1198-1206
106. Madhu C, Klaassen CD 1991 Protective effect of pregnenolone-16α-carbonitrile on acetaminophen-induced hepatotoxicity in hamsters. Toxicol Appl Pharmacol 109:305-313
107. Hosokawa M, Hattori K, Satoh T 1993 Differential responses of rat hepatic microsomal carboxylesterase isozymes to glucocorticoids and pregnenolone 16α-carbonitrile. Biochem Pharmacol 45:2317-2322
108. Courtois A, Payen L, Guillouzo A, Fardel O 1999 Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone. FEBS Lett 459:381-385
109. Fromm MF, Kauffmann HM, Fritz P, Burk O, Kroemer HK, Warzok RW, Eichelbaum M, Siegmund W, Schrenk D 2000 The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 157:1575-1580
110. Kullak-Ublick GA, Stieger B, Hagenbuch B, Meier PJ 2000 Hepatic transport of bile salts. Semin Liver Dis 20:273-292
111. Stieger B, Meier PJ 1998 Bile acid and xenobiotic transporters in liver. Curr Opin Cell Biol 10:462-467
112. Durr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K 2000 St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68:598-604
113. Ernst E 1999 Second thoughts about safety of St John's wort. Lancet 354:2014-2016
114. Ernst E, Rand JI, Barnes J, Stevinson C 1998 Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 54:589-594
115. Breidenbach T, Hoffmann MW, Becker T, Schlitt H, Klempnauer J 2000 Drug interaction of St John's wort with cyclosporin. Lancet 355:1912
116. Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I 1999 Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 66:338-345
117. Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G 2000 Acure heart transplant rejection due to Saint John's wort. Lancet 355:548-549
118. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA 2000 St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 97:7500-7502
119. Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK 2000 St John's wort, a herbal antidepressant, activates the steroid X receptor. J Endocrinol 166:R11-R16
120. Laakmann G, Schule C, Baghai T, Kieser M 1998 St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry 31(Suppl 1):54-59
121. Watkins PB, Whitcomb RW 1998 Hepatic dysfunction associated with troglitazone. N Engl J Med 338:916-917
122. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B 1999 Identification of a nuclear receptor for bile acids. Science 284:1362-1365
123. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM 1999 Bile acids: natural ligands for an orphan nuclear receptor. Science 284:1365-1368
124. Wang H, Chen J, Hollister K, Sowers LC, Forman BM 1999 Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell 3:543-553
125. Grober J, Zaghini I, Fujii H, Jones SA, Kliewer SA, Willson TM, Ono T, Besnard P 1999 Identification of a bile acid-responsive element in the human ileal bile acid-binding protein gene. Involvement of the farnesoid X receptor/9-cis-retinoic acid receptor heterodimer. J Biol Chem 274:29749-29754
126. Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ 2001 Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem 276:28857-28865
127. Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G, Gonzalez FJ 2000 Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102:731-744
128. Russell DW 1999 Nuclear orphan receptors control cholesterol catabolism. Cell 97:539-542
129. Einarsson K, Gustafsson JA 1973 Effects of a potent catatoxic steroid, 16-cyanopregnenolone, on microsomal metabolism of steroid hormones, sterols and bile acids in rats. Eur J Biochem 32:197-206
130. Li YC, Wang DP, Chiang JY 1990 Regulation of cholesterol 7α-hydroxylase in the liver. Cloning, sequencing, and regulation of cholesterol 7α-hydroxylase mRNA. J Biol Chem 265:12012-12019
131. Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, Evans RM 2001 An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA 98:3375-3380
132. Javitt NB 1966 Cholestasis in rats induced by taurolithocholate. Nature 210:1262-1263
133. Setchell KD, Rodrigues CM, Clerici C, Solinas A, Morelli A, Gartung C, Boyer J 1997 Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology 112:226-235
134. Selye H 1972 Prevention by catatoxic steroids of lithocholic acid-induced biliary concrements in the rat. Proc Soc Exp Biol Med 141:555-558
135. Bremmelgaard A, Sjovall J 1979 Bile acid profiles in urine of patients with liver diseases. Eur J Clin Invest 9:341-348
136. Araya Z, Wikvall K 1999 6α-Hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes. Biochim Biophys Acta 1438:47-54
137. Bachs L, Pares A, Elena M, Piera C, Rodes J 1989 Comparison of rifampicin with phenobarbitone for treatment of pruritus in biliary cirrhosis. Lancet 1:574-576
138. Cancado EL, Leitao RM, Carrilho FJ, Laudanna AA 1998 Unexpected clinical remission of cholestasis after rifampicin therapy in patients with normal or slightly increased levels of γ-glutamyl transpeptidase. Am J Gastroenterol 93:1510-1517
139. Gillespie DA, Vickers CR 1993 Pruritus and cholestasis: therapeutic options. J Gastroenterol Hepatol 8:168-173
140. Ozturk Y, Aydin S, Baser KHC, Kirimer N, Kurtar-Ozturk N 1992 Hepatoprotective activity of Hypericim perforatum L. alcoholic extract in rodents. Phytother Res 6:44-46
141. Chevallier A 1996 The encyclopedia of medicinal plants. London: Dorling-Kindersley Limited
142. Schuetz EG, Strom S, Yasuda K, Lecureur V, Assem M, Brimer C, Lamba J, Kim RB, Ramachandran V, Komoroski BJ, Venkataramanan R, Cai H, Sinal CJ, Gonzalez FJ, Schuetz JD 2001 Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters and cytochrome P450. J Biol Chem 276:39411-39418
143. Baes M, Gulick T, Choi HS, Martinoli MG, Simha D, Moore DD 1994 A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 14:1544-1551
144. Forman BM, Tzameli I, Choi HS, Chen J, Simha D, Seol W, Evans RM, Moore DD 1998 Androstane metabolites bind to and deactivate the nuclear receptor CAR-β. Nature 395:612-615
145. Wei P, Zhang J, Egan-Haffey M, Liang S, Moore DD 2000 The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism. Nature 407:920-923
146. Honkakoski P, Zelko I, Sueyoshi T, Negishi M 1998 The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol Cell Biol 18:5652-5658
147. Kawamoto T, Sueyoshi T, Zelko I, Moore R, Washburn K, Negishi M 1999 Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol Cell Biol 19:6318-6322
148. Honkakoski P, Moore R, Washburn KA, Negishi M 1998 Activation by diverse xenochemicals of the 51-base pair phenobarbital-responsive enhancer module in the CYP2B10 gene. Mol Pharmacol 53:597-601
149. Smirlis D, Muangmoonchai R, Edwards M, Phillips IR, Shephard EA 2001 Orphan receptor promiscuity in the induction of cytochromes P450 by xenobiotics. J Biol Chem 276:12822-12826
150. Sueyoshi T, Kawamoto T, Zelko I, Honkakoski P, Negishi M 1999 The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. J Biol Chem 274:6043-6046
151. Tzameli I, Pissios P, Schuetz EG, Moore DD 2000 The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR. Mol Cell Biol 20:2951-2958
152. Rochel N, Tocchini-Valentini G, Egea PF, Juntunen K, Garnier JM, Vihko P, Moras D 2001 Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor. Eur J Biochem 268:971-979
153. Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D 2000 The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell 5:173-179
154. Harvey JL, Paine AJ, Maurel P, Wright MC 2000 Effect of the adrenal 11-β-hydroxylase inhibitor metyrapone on human hepatic cytochrome P-450 expression: induction of cytochrome P-450 3A4. Drug Metab Dispos 28:96-101
155. Bertilsson G, Berkenstam A, Blomquist P 2001 Functionally conserved xenobiotic responsive enhancer in cytochrome P450 3A7. Biochem Biophys Res Commun 280:139-144