A structural view of nuclear hormone receptor: Endocrine disruptor interactions

Cellular and Molecular Life Sciences

Volumn 67, Issue 8, 2010, Pages 1219-1237

  Le Maire, Albane ^a   Bourguet, W ^a   Balaguer, Patrick ^b,c,d  

^a CENTRE DE BIOCHIMIE STRUCTURALE   (France)

^b INSTITUT DE RECHERCHE EN CANCÉROLOGIE DE MONTPELLIER   (France)

^c UNIV MONTPELLIER   (France)

^d CENTRE VAL D AURELLE   (France)

Author keywords

Crystal structures; Endocrine disrupting chemicals; Environmental pollutants; Hormone; Nuclear hormone receptors

Indexed keywords

DIETHYLSTILBESTROL; ENDOCRINE DISRUPTOR; ESTROGEN RECEPTOR; HORMONE RECEPTOR; LIGAND; NUCLEAR HORMONE RECEPTOR; ORGANOTIN COMPOUND; PREGNANE X RECEPTOR; RETINOID X RECEPTOR; UNCLASSIFIED DRUG; XENOBIOTIC AGENT; XENOESTROGEN; XENOREXINOID; CELL RECEPTOR;

CRYSTAL STRUCTURE; HORMONE RECEPTOR INTERACTION; HUMAN; LIGAND BINDING; MOLECULAR MECHANICS; NONHUMAN; PROTEIN BINDING; PROTEIN DATABASE; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; TOXICITY TESTING; ANIMAL; CHEMISTRY; DRUG EFFECT; ENDOCRINE SYSTEM; METABOLISM;

ANIMALS; ENDOCRINE DISRUPTORS; ENDOCRINE SYSTEM; HUMANS; RECEPTORS, CYTOPLASMIC AND NUCLEAR;

EID: 77950620887     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-009-0249-2     Document Type: Review

References (147)

1. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC (2009) Endocrinedisrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 30:293-342
2. Hotchkiss AK, Rider CV, Blystone CR, Wilson VS, Hartig PC, Ankley GT, Foster PM, Gray CL, Gray LE (2008) Fifteen years after "Wingspread": environmental endocrine disrupters and human and wildlife health: where we are today and where we need to go. Toxicol Sci 105:235-259
3. Swedenborg E, Ruegg J, Makela S, Pongratz I (2009) Endocrine disruptive chemicals: mechanisms of action and involvement in metabolic disorders. J Mol Endocrinol 43:1-10
4. Tabb MM, Blumberg B (2006) New modes of action for endocrine-disrupting chemicals. Mol Endocrinol 20:475-482
5. Janosek J, Hilscherova K, Blaha L, Holoubek I (2006) Environmental xenobiotics and nuclear receptors: interactions, effects and in vitro assessment. Toxicol In Vitro 20:18-37
6. Toppari J (2008) Environmental endocrine disrupters. Sex Dev 2:260-267
7. Herbst AL, Ulfelder H, Poskanzer DC (1971) Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 284:878-881
8. Gronemeyer H, Gustafsson JA, Laudet V (2004) Principles for modulation of the nuclear receptor superfamily. Nat Rev Drug Discov 3:950-964
9. Germain P, Staels B, Dacquet C, Spedding M, Laudet V (2006) Overview of nomenclature of nuclear receptors. Pharmacol Rev 58:685-704
10. Bourguet W, Germain P, Gronemeyer H (2000) Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications. Trends Pharmacol Sci 21:381-388
11. Pike AC (2006) Lessons learnt from structural studies of the oestrogen receptor. Best Pract Res Clin Endocrinol Metab 20:1-14
12. Renaud JP, Moras D (2000) Structural studies on nuclear receptors. Cell Mol Life Sci 57:1748-1769
13. Couse JF, Korach KS (1999) Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 20:358-417
14. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863-870
15. Curtis SW, Washburn T, Sewall C, DiAugustine R, Lindzey J, Couse JF, Korach KS (1996) Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Proc Natl Acad Sci USA 93:12626-12630
16. Liu MM, Albanese C, Anderson CM, Hilty K, Webb P, Uht RM, Price RH Jr, Pestell RG, Kushner PJ (2002) Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression. J Biol Chem 277:24353-24360
17. Pettersson K, Delaunay F, Gustafsson JA (2000) Estrogen receptor beta acts as a dominant regulator of estrogen signaling. Oncogene 19:4970-4978
18. Weihua Z, Saji S, Makinen S, Cheng G, Jensen EV, Warner M, Gustafsson JA (2000) Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus. Proc Natl Acad Sci USA 97:5936-5941
19. Lindberg MK, Moverare S, Static S, Gao H, Dahlman-Wright K, Gustafsson JA, Ohlsson C (2003) Estrogen receptor (ER)beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice. Mol Endocrinol 17:203-208
20. Ogawa S, Eng V, Taylor J, Lubahn DB, Korach KS, Pfaff DW (1998) Roles of estrogen receptor-alpha gene expression in reproduction-related behaviors in female mice. Endocrinology 139:5070-5081
21. Nahoum V, Bourguet W (2007) Androgen and estrogen receptors: potential of crystallography in the fight against cancer. Int J Biochem Cell Biol 39:1280-1287
22. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252-4263
23. Veeneman GH (2005) Non-steroidal subtype selective estrogens. Curr Med Chem 12:1077-1136
24. Kaufman RH, Korhonen MO, Strama T, Adam E, Kaplan A (1982) Development of clear cell adenocarcinoma in DES-exposed offspring under observation. Obstet Gynecol 59:68S-72S
25. Herbst AL (1981) The current status of the DES-exposed population. Obstet Gynecol Annu 10:267-278
26. Newbold R (1995) Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens. Environ Health Perspect 103(Suppl 7):7-83
27. Cargouet M, Perdiz D, Mouatassim-Souali A, Tamisier-Karolak S, Levi Y (2004) Assessment of river contamination by estrogenic compounds in Paris area (France). Sci Total Environ 324:55-66
28. Ribeiro C, Tiritan ME, Rocha E, Rocha MJ (2009) Seasonal and spatial distribution of several endocrine-disrupting compounds in the Douro River Estuary, Portugal. Arch Environ Contam Toxicol 56:1-11
29. Ying GG, Kookana RS, Kumar A, Mortimer M (2009) Occurrence and implications of estrogens and xenoestrogens in sewage effluents and receiving waters from South East Queensland. Sci Total Environ 407:5147-5155
30. Takemura H, Shim JY, Sayama K, Tsubura A, Zhu BT, Shimoi K (2007) Characterization of the estrogenic activities of zearalenone and zeranol in vivo and in vitro. J Steroid Biochem Mol Biol 103:170-177
31. Trenholm HL, Warner RM, Fitzpatrick DW (1984) Rapid, sensitive liquid chromatographic method for determination of zearalenone and alpha- and beta-zearalenol in wheat. J Assoc Off Anal Chem 67:968-972
32. Veldman A, Borggreve GJ, Mulders EJ, van de Lagemaat D (1992) Occurrence of the mycotoxins ochratoxin A, zearalenone and deoxynivalenol in feed components. Food Addit Contam 9:647-655
33. Kiessling KH, Pettersson H (1978) Metabolism of zearalenone in rat liver. Acta Pharmacol Toxicol (Copenh) 43:285-290
34. Kuiper-Goodman T, Scott PM, Watanabe H (1987) Risk assessment of the mycotoxin zearalenone. Regul Toxicol Pharmacol 7:253-306
35. Messina M, Kucuk O, Lampe JW (2006) An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels. J AOAC Int 89:1121-1134
36. Escande A, Pillon A, Servant N, Cravedi JP, Larrea F, Muhn P, Nicolas JC, Cavailles V, Balaguer P (2006) Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta. Biochem Pharmacol 71:1459-1469
37. Lauber SN, Ali S, Gooderham NJ (2004) The cooked food derived carcinogen 2-amino-l-methyl-6-phenylimidazo[4, 5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissuespecific carcinogenicity. Carcinogenesis 25:2509-2517
38. Nettles KW, Bruning JB, Gil G, Nowak J, Sharma SK, Hahm JB, Kulp K, Hochberg RB, Zhou H, Katzenellenbogen JA, Katzenellenbogen BS, Kim Y, Joachmiak A, Greene GL (2008) NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses. Nat Chem Biol 4:241-247
39. Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R (2006) Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci 79:1160-1169
40. Paris F, Balaguer P, Terouanne B, Servant N, Lacoste C, Cravedi JP, Nicolas JC, Sultan C (2002) Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines. Mol Cell Endocrinol 193:43-49
41. Bouskine A, Nebout M, Brucker-Davis F, Benahmed M, Fenichel P (2009) Low doses of bisphenol A promote human seminoma cell proliferation by activating PKA and PKG via a membrane G-protein-coupled estrogen receptor. Environ Health Perspect 117:1053-1058
42. Okada H, Tokunaga T, Liu X, Takayanagi S, Matsushima A, Shimohigashi Y (2008) Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma. Environ Health Perspect 116:32-38
43. Ying GG, Williams B, Kookana R (2002) Environmental fate of alkylphenols and alkylphenol ethoxylates: a review. Environ Int 28:215-226
44. Kunz PY, Galicia HF, Fent K (2006) Comparison of in vitro and in vivo estrogenic activity of UV filters in fish. Toxicol Sci 90:349-361
45. Molina-Molina JM, Escande A, Pillon A, Gomez E, Pakdel F, Cavailles V, Olea N, Ait-Aissa S, Balaguer P (2008) Profiling of benzophenone derivatives using fish and human estrogen receptor-specific in vitro bioassays. Toxicol Appl Pharmacol 232:384-395
46. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753-758
47. Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL (1998) The structural basis of estrogen receptor/ coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95:927-937
48. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S (1998) Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/ antagonists. Mol Pharmacol 54:105-112
49. Manas ES, Xu ZB, Unwalla RJ, Somers WS (2004) Understanding the selectivity of genistein for human estrogen receptor-beta using X-ray crystallography and computational methods. Structure 12:2197-2207
50. Pike AC, Brzozowski AM, Hubbard RE, Bonn T, Thorsell AG, Engstrom O, Ljunggren J, Gustafsson JA, Carlquist M (1999) Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO J 18:4608-4618
51. Vivat V, Gofflo D, Garcia T, Wurtz JM, Bourguet W, Philibert D, Gronemeyer H (1997) Sequences in the ligand-binding domains of the human androgen and progesterone receptors which determine their distinct ligand identities. J Mol Endocrinol 18:147-160
52. Nettles KW, Sun J, Radek JT, Sheng S, Rodriguez AL, Katzenellenbogen JA, Katzenellenbogen BS, Greene GL (2004) Allosteric control of ligand selectivity between estrogen receptors alpha and beta: implications for other nuclear receptors. Mol. Cell 13:317-327
53. Nahoum V, Perez E, Germain P, Rodriguez-Barrios F, Manzo F, Kammerer S, Lemaire G, Hirsch O, Royer CA, Gronemeyer H, de Lera AR, Bourguet W (2007) Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function. Proc Natl Acad Sci USA 104:17323-17328
54. Smith CL, O'Malley BW (2004) Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev 25:45-71
55. Giguere V (2002) To ERR in the estrogen pathway. Trends Endocrinol Metab 13:220-225
56. Bonnelye E, Vanacker JM, Dittmar T, Begue A, Desbiens X, Denhardt DT, Aubin JE, Laudet V, Foumier B (1997) The ERR-I orphan receptor is a transcriptional activator expressed during bone development. Mol Endocrinol 11:905-916
57. Horard B, Vanacker JM (2003) Estrogen receptor-related receptors: orphan receptors desperately seeking a ligand. J Mol Endocrinol 31:349-357
58. Vanacker JM, Pettersson K, Gustafsson JA, Laudet V (1999) Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta. EMBO J 18:4270-4279
59. Lu D, Kiriyama Y, Lee KY, Giguere V (2001) Transcriptional regulation of the estrogen-inducible pS2 breast cancer marker gene by the ERR family of orphan nuclear receptors. Cancer Res 61:6755-6761
60. Yu S, Wang X, Ng CF, Chen S, Chan FL (2007) ERRgamma suppresses cell proliferation and tumor growth of androgensensitive and androgen-insensitive prostate cancer cells and its implication as a therapeutic target for prostate cancer. Cancer Res 67:4904-4914
61. Ariazi EA, Jordan VC (2006) Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem 6:203-215
62. Giguere V (2008) Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev 29:677-696
63. Baillie-Hamilton PF (2002) Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 8:185-192
64. Li J, Ma M, Wang Z (2009). In vitro profiling of endocrine disrupting effects of phenols. Toxicol In Vitro (in press)
65. Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP (2002) Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell 9:303-313
66. Yang C, Chen S (1999) Two organochlorine pesticides, toxaphene and chlordane, are antagonists for estrogen-related receptor alpha-1 orphan receptor. Cancer Res 59:4519-4524
67. Coward P, Lee D, Hull MV, Lehmann JM (2001) 4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma. Proc Natl Acad Sci USA 98:8880-8884
68. Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguere V (2001) Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev 15:833-838
69. Wang J, Fang F, Huang Z, Wang Y, Wong C (2009) Kaempferol is an estrogen-related receptor alpha and gamma inverse agonist. FEBS Lett 583:643-647
70. Suetsugi M, Su L, Karlsberg K, Yuan YC, Chen S (2003) Flavone and isoflavone phytoestrogens are agonists of estrogenrelated receptors. Mol Cancer Res 1:981-991
71. Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT (2006) X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation. J Biol Chem 281:37773-37781
72. Abad MC, Askari H, O'Neill J, Klinger AL, Milligan C, Lewandowski F, Springer B, Spurlino J, Rentzeperis D (2008) Structural determination of estrogen-related receptor gamma in the presence of phenol derivative compounds. J Steroid Biochem Mol Biol 108:44-54
73. Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y (2007) Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma. J Biochem 142:517-524
74. Matsushima A, Teramoto T, Okada H, Liu X, Tokunaga T, Kakuta Y, Shimohigashi Y (2008) ERRgamma tethers strongly bisphenol A and 4-alpha-cumylphenol in an induced-fit manner. Biochem Biophys Res Commun 373:408-413.
75. Kallen J, Schlaeppi JM, Bitsch F, Filipuzzi I, Schilb A, Riou V, Graham A, Strauss A, Geiser M, Foumier B (2004) Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1 alpha. J Biol Chem 279:49330-49337
76. Greschik H, Flaig R, Renaud JP, Moras D (2004) Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity. J Biol Chem 279:33639-33646
77. Orans J, Teotico DG, Redinbo MR (2005) The nuclear xenobiotic receptor pregnane X receptor: recent insights and new challenges. Mol Endocrinol 19:2891-2900
78. Biswas A, Mani S, Redinbo MR, Krasowski MD, Li H, Ekins S (2009) Elucidating the 'Jekyll and Hyde' nature of PXR: the case for discovering antagonists or allosteric antagonists. Pharm Res 26:1807-1815
79. Moreau A, Vilarem MJ, Maurel P, Pascussi JM (2008) Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 5:35-41
80. Mikamo E, Harada S, Nishikawa J, Nishihara T (2003) Endocrine disrupters induce cytochrome P450 by affecting transcriptional regulation via pregnane X receptor. Toxicol Appl Pharmacol 193:66-72
81. Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR (2003) Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor. J Mol Biol 331:815-828
82. Masuyama H, Suwaki N, Tateishi Y, Nakatsukasa H, Segawa T, Hiramatsu Y (2005) The pregnane X receptor regulates gene expression in a ligand- and promoter-selective fashion. Mol Endocrinol 19:1170-1180
83. Benod C, Subra G, Nahoum V, Mallavialle A, Guichou JF, Milhau J, Roblés S, Bourguet W, Pascussi JM, Balaguer P, Chavanieu A (2008) N-1H-Benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists. Bioorg Med Chem 16:3537-3549
84. Lemaire G, Benod C, Nahoum V, Pillon A, Boussioux AM, Guichou JF, Subra G, Pascussi JM, Bourguet W, Chavanieu A, Balaguer P (2007) Discovery of a highly active ligand of human pregnane x receptor: a case study from pharmacophore modeling and virtual screening to "in vivo" biological activity. Mol Pharmacol 72:572-581
85. 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
86. Xue Y, Chao E, Zuercher WJ, Willson TM, Collins JL, Redinbo MR (2007) Crystal structure of the PXR-T1317 complex provides a scaffold to examine the potential for receptor antagonism. Bioorg Med Chem 15:2156-2166
87. Xue Y, Moore LB, Orans J, Peng L, Bencharit S, Kliewer SA, Redinbo MR (2007) Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol. Endocrinol 21:1028-1038
88. Bertilsson G, Berkenstam A, Blomquist P (2001) Functionally conserved xenobiotic responsive enhancer in cytochrome P450 3A7. Biochem Biophys Res Commun 280:139-144
89. Blumberg B, Sabbagh W Jr, Juguilon H, Bolado J Jr, van Meter CM, Ong ES, Evans RM (1998) SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Dev 12:3195-3205
90. 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
91. Lemaire G, Mnif W, Pascussi JM, Pillon A, Rabenoelina F, Fenet H, Gomez E, Casellas C, Nicolas JC, Cavailles V, Duchesne MJ, Balaguer P (2006) Identification of new human pregnane X receptor ligands among pesticides using a stable reporter cell system. Toxicol Sci 91:501-509
92. 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
93. Synold TW, Dussault I, Forman BM (2001) The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 7:584-590
94. Watkins RE, Maglich JM, Moore LB, Wisely GB, Noble SM, Davis-Searles PR, Lambert MH, Kliewer SA, Redinbo MR (2003) 2.1 Å crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry 42:1430-1438
95. Moore JT, Kliewer SA (2000) Use of the nuclear receptor PXR to predict drug interactions. Toxicology 153:1-10
96. 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
97. di Masi A, Marinis ED, Ascenzi P, Marino M (2009). Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects. Mol Aspects Med (in press)
98. Jacobs MN, Nolan GT, Hood SR (2005) Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol 209:123-133
99. Mnif W, Pascussi JM, Pillon A, Escande A, Bartegi A, Nicolas JC, Cavailles V, Duchesne MJ, Balaguer P (2007) Estrogens and antiestrogens activate hPXR. Toxicol Lett 170:19-29
100. Kinani S, Bouchonnet S, Creusot N, Bourcier S, Balaguer P, Porcher JM, Ait-Aissa S (2010) Multiple endocrine activities in sediments from small rivers in North of France assessed by the combined use of in vitro bioassays and chemical analysis. Environ Pollut 158:74-83
101. Tabb MM, Kholodovych V, Grun F, Zhou C, Welsh WJ, Blumberg B (2004) Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR). Environ Health Perspect 112:163-169
102. Pacyniak EK, Cheng X, Cunningham ML, Crofton K, Klaassen CD, Guo GL (2007) The flame retardants, polybrominated diphenyl ethers, are pregnane X receptor activators. Toxicol Sci 97:94-102
103. Chrencik JE, Orans J, Moore LB, Xue Y, Peng L, Collins JL, Wisely GB, Lambert MH, Kliewer SA, Redinbo MR (2005) Structural disorder in the complex of human pregnane X receptor and the macrolide antibiotic rifampicin. Mol. Endocrinol 19:1125-1134
104. Teotico DG, Bischof JJ, Peng L, Kliewer SA, Redinbo MR (2008) Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Mol Pharmacol 74:1512-1520
105. Kretschmer XC, Baldwin WS (2005) CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact 155:111-128
106. di Masi A, Marinis ED, Ascenzi P, Marino M (2009) Nuclear receptors CAR and PXR: molecular, functional, and biomedical aspects. Mol Aspects Med 30:297-343
107. Mangelsdorf DJ, Evans RM (1995) The RXR heterodimers and orphan receptors. Cell 83:841-850
108. Germain P, Iyer J, Zechel C, Gronemeyer H (2002) Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature 415:187-192
109. Chen JY, Clifford J, Zusi C, Starrett J, Tortolani D, Ostrowski J, Reczek PR, Chambon P, Gronemeyer H (1996) Two distinct actions of retinoid-receptor ligands. Nature 382:819-822
110. Botling J, Castro DS, Oberg F, Nilsson K, Perlmann T (1997) Retinoic acid receptor/retinoid X receptor heterodimers can be activated through both subunits providing a basis for synergistic transactivation and cellular differentiation. J Biol Chem 272:9443-9449
111. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68:397-406
112. de Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T (2000) Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 290:2140-2144
113. de Lera AR, Bourguet W, Altucci L, Gronemeyer H (2007) Design of selective nuclear receptor modulators: RAR and RXR as a case study. Nat Rev Drug Discov 6:811-820
114. Nakanishi T (2008) Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor. J Toxicol Sci 33:269-276
115. Grun F, Blumberg B (2006) Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 147:S50-S55
116. Grun F, Blumberg B (2009) Endocrine disrupters as obesogens. Mol Cell Endocrinol 304:19-29
117. Antizar-Ladislao B (2008) Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment: a review. Environ Int 34:292-308
118. Grun F, Watanabe H, Zamanian Z, Maeda L, Arima K, Cubacha R, Gardiner DM, Kanno J, Iguchi T, Blumberg B (2006) Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol Endocrinol 20:2141-2155
119. Kanayama T, Kobayashi N, Mamiya S, Nakanishi T, Nishikawa J (2005) Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway. Mol Pharmacol 67:766-774
120. Castro LF, Lima D, Machado A, Melo C, Hiromori Y, Nishikawa J, Nakanishi T, Reis-Henriques MA, Santos MM (2007) Imposex induction is mediated through the Retinoid X Receptor signalling pathway in the neogastropod Nucella lapillus. Aquat Toxicol 85:57-66
121. Nishikawa J, Mamiya S, Kanayama T, Nishikawa T, Shiraishi F, Horiguchi T (2004) Involvement of the retinoid X receptor in the development of imposex caused by organotins in gastropods. Environ Sci Technol 38:6271-6276
122. le Maire A, Grimaldi M, Roecklin D, Dagnino S, Vivat-Hannah V, Balaguer P, Bourguet W (2009) Activation of RXR-PPAR heterodimers by organotin environmental endocrine disrupters. EMBO Rep 10:367-373
123. Harmon MA, Boehm MF, Heyman RA, Mangelsdorf DJ (1995) Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. Proc Natl Acad Sci USA 92:6157-6160
124. Li J, Ma M, Wang Z (2008) A two-hybrid yeast assay to quantify the effects of xenobiotics on retinoid X receptor-mediated gene expression. Toxicol Lett 176:198-206
125. Svensson S, Ostberg T, Jacobsson M, Norstrom C, Stefansson K, Hallen D, Johansson IC, Zachrisson K, Ogg D, Jendeberg L (2003) Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation. EMBO J 22:4625-4633
126. Egea PF, Mitschler A, Rochel N, Ruff M, Chambon P, Moras D (2000) Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid. EMBO J 19:2592-2601
127. Pogenberg V, Guichou JF, Vivat-Hannah V, Kammerer S, Perez E, Germain P, de Lera AR, Gronemeyer H, Royer CA, Bourguet W (2005) Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies. J Biol Chem 280:1625-1633
128. Nettles KW, Bruning JB, Gil G, O'Neill EE, Nowak J, Guo Y, Kim Y, DeSombre ER, Dilis R, Hanson RN, Joachimiak A, Greene GL (2007) Structural plasticity in the oestrogen receptor ligand-binding domain. EMBO Rep 8:563-568
129. Gumy C, Chandsawangbhuwana C, Dzyakanchuk AA, Kratschmar DV, Baker ME, Odermatt A (2008) Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production. PLoS One 3:e3545
130. Witorsch RJ (2002) Endocrine disrupters: can biological effects and environmental risks be predicted? Regul Toxicol Pharmacol 36:118-130
131. de Fur PL (2004) Use and role of invertebrate models in endocrine disruptor research and testing. ILAR J 45:484-493
132. Roncaglioni A, Benfenati E (2008) In silico-aided prediction of biological properties of chemicals: oestrogen receptor-mediated effects. Chem Soc Rev 37:441-450
133. Waller CL, Juma BW, Gray LE Jr, Kelce WR (1996) Threedimensional quantitative structure-activity relationships for androgen receptor ligands. Toxicol Appl Pharmacol 137:219-227
134. Jacobs MN (2004) In silico tools to aid risk assessment of endocrine disrupting chemicals. Toxicology 205:43-53
135. Devillers J, Marchand-Geneste N, Carpy A, Porcher JM (2006) SAR and QSAR modeling of endocrine disrupters. SAR QSAR Environ Res 17:393-412
136. Fang H, Tong W, Branham WS, Moland CL, Dial SL, Hong H, Xie Q, Perkins R, Owens W, Sheehan DM (2003) Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor. Chem Res Toxicol 16:1338-1358
137. Ekins S, Chang C, Mani S, Krasowski MD, Reschly EJ, Iyer M, Kholodovych V, Ai N, Welsh WJ, Sinz M, Swaan PW, Patel R, Bachmann K (2007) Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites. Mol Pharmacol 72:592-603
138. D'Ursi P, Salvi E, Fossa P, Milanesi L, Rovida E (2005) Modelling the interaction of steroid receptors with endocrine disrupting chemicals. BMC Bioinformatics 6(Suppl 4):S10
139. Celik L, Davey J, Lund D, Schiott B (2008) Exploring interactions of endocrine-disrupting compounds with different conformations of the human estrogen receptor alpha ligand binding domain: a molecular docking study. Chem Res Toxicol 21:2195-2206
140. Marchand-Geneste N, Cazaunau M, Carpy AJ, Laguerre M, Porcher JM, Devillers J (2006) Homology model of the rainbow trout estrogen receptor (rtERalpha) and docking of endocrine disrupting chemicals (EDCs). SAR QSAR Environ Res 17:93-105
141. Lill MA, Winiger F, Vedani A, Ernst B (2005) Impact of induced fit on ligand binding to the androgen receptor: a multidimensional QSAR study to predict endocrine-disrupting effects of environmental chemicals. J Med Chem 48:5666-5674
142. Sivanesan D, Rajnarayanan RV, Doherty J, Pattabiraman N (2005) In-silico screening using flexible ligand binding pockets: a molecular dynamics-based approach. J Comput Aided Mol Des 19:213-228
143. Zavodszky MI, Lei M, Thorpe MF, Day AR, Kuhn LA (2004) Modeling correlated main-chain motions in proteins for flexible molecular recognition. Proteins 57:243-261
144. Bennion BJ, Cosman M, Lightstone FC, Knize MG, Montgomery JL, Bennett LM, Felton JS, Kulp KS (2005) PhIP carcinogenicity in breast cancer: computational and experimental evidence for competitive interactions with human estrogen receptor. Chem Res Toxicol 18:1528-1536
145. Kim Y, Koh M, Kim DK, Choi HS, Park SB (2009) Efficient discovery of selective small molecule agonists of estrogenrelated receptor gamma using combinatorial approach. J Comb Chem 11:928-937
146. Nose T, Shimohigashi Y (2008) A docking modelling rationally predicts strong binding of bisphenol A to estrogen-related receptor gamma. Protein Pept Lett 15:290-296
147. Härtung T, Rovida C (2009) Chemical regulators have overreached. Nature 460:1080-1081