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Steroid hormone receptors and dietary ligands: a selected review

Published online by Cambridge University Press:  28 February 2007

David F. V. Lewis
Affiliation:
School of Biomedical and Life Sciences, University of Surrey, Guildford GU2 7XH, UK
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Abstract

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Members of the nuclear steroid hormone superfamily mediate essential physiological functions. Steroid hormone receptors (SHR) act directly on DNA, regulate the synthesis of their target genes and are usually activated by ligand binding. Both endogenous and exogenous compounds and their metabolites may act as activators of SHR and disruptors of endocrine, cellular and lipid homeostasis. The endogenous ligands are generally steroids such as 17β-oestradiol, androgens, progesterone and pregnenolone. The exogenous compounds are usually delivered through the diet and include non-steroidal ligands. Examples of such ligands include isoflavanoids or phyto-oestrogens, and food contaminants such as exogenous oestrogens from hormone-treated cattle, pesticides, polychlorinated biphenyls and plasticisers. Certain drugs are also ligands; so nuclear receptors are also important drug targets for intervention in disease processes. The present review summarises recent reports on ligand-activated SHR that describe the selective regulation of a tightly-controlled cross-talking network involving exchange of ligands, and the control of major classes of cytochrome P450 (CYP) isoforms which metabolise many bioactive exogenous compounds. Many CYP have broad substrate activity and appear to be integrated into a coordinated metabolic pathway, such that whilst some receptors are ligand specific, other sensors may have a broader specificity and low ligand affinity to monitor aggregate levels of inducers. They can then trigger production of metabolising enzymes to defend against possible toxic nutrients and xenobiotic compounds. The influence of dietary intakes of nutrients and non-nutrients on the human oestrogen receptors (α and β), the aryl hydrocarbon receptor, the pregnane X receptor, the constitutive androstane receptor, and the peroxisome proliferator-activated receptors (α and γ), can be examined by utilising computer-generated molecular models of the ligand–receptor interaction, based on information generated from crystallographic data and sequence homology. In relation to experimental and observed data, molecular modelling can provide a scientifically sound perspective on the potential risk and benefits to human health from dietary exposure to hormone-mimicking chemicals, providing a useful tool in drug development and in a situation of considerable public concern.

Type
Meeting Report
Copyright
Copyright © The Nutrition Society 2002

References

Abbott, BD, Schmid, JE, Pitt, JA, Buckalew, AR, Wood, CR, Held, GA & Diliberto, JJ (1999) Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse. Toxicology and Applied Pharmacology 155, 6270.CrossRefGoogle ScholarPubMed
Adami, H-O, Bergström, R, Möhner, M, Zatonski, W, Storm, H, Ekbom, A, Tretli, S, Teppo, L, Zeigler, H, Rahu, M, Gurevicius, R & Stengrevics, A (1994) Testicular cancer in nine northern European countries. International Journal of Cancer 59, 3338.CrossRefGoogle ScholarPubMed
Adlercrutz, H (1998) Evolution, nutrition, intestinal microflora and prevention of cancer: A hypothesis. Proceedings of the Society of Experimental Biology and Medicine 217, 241246.CrossRefGoogle Scholar
Ahlborg, UG, Lipworth, L, Titus-Ernstoff, L, Hsieh, C-C, Hanberg, A, Baron, J, Trichopolous, DM & Adami, H-O (1995) Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: An assessment of the biological and epidemiological evidence. Critical Reviews in Toxicology 25, 463531.CrossRefGoogle ScholarPubMed
Alberts, B, Bray, D, Johnson, A, Lewis, J, Raff, M, Roberts, K & Walter, P (1997) Essential Cell Biology. New York and London: Garland Publishing.Google Scholar
Andersson, A-M & Skakkebæk, NE (1999) Exposure to exogenous estrogens in food: possible impact on human development and health. European Journal of Endocrinology 140, 477485.Google Scholar
Anonymous (1999) Hormone studies flawed, researcher warns. Chemistry and Industry 18 October issue, 784.Google Scholar
Arnold, SF, Klotz, DM, Collins, BM, Vonier, PM, Guillette, LJ Jr & McLachlan, JA (1996) Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272, 14891492.CrossRefGoogle ScholarPubMed
Arnold, SF, Vonier, PM, Collins, BM, Klotz, DM, Guillette, LJ Jr & McLachlan, JR (1997). In vitro synergistic interaction of alligator and human estrogen receptors with combinations of environmental chemicals. Environmental Health Perspectives 105, 615632.Google ScholarPubMed
Ashby, J (2001) Testing for endocrine disruption post EDSTAC: extrapolation from low dose rodent effects to humans. Toxicology Letters 120, 233242.CrossRefGoogle ScholarPubMed
Ashby, J, Tinwell, H, Soames, A & Foster, J (1999) Induction of hyperplasia and increased DNA content in the uterus of immature rats exposed to coumestrol,. Environmental Health Perspectives 107, 819822.CrossRefGoogle ScholarPubMed
Auger, J, Kunstmann, JM, Czyglik, F & Jouannet, P (1995) Decline in semen quality among fertile men in Paris during the past 20 years. New England Journal of Medicine 332, 281285.CrossRefGoogle ScholarPubMed
Baes, M, Gulick, T, Choi, H-S, 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. Molecular and Cellular Biology 14, 15441552.Google Scholar
Barkhem, T, Carlsson, B, Nilsson, Y, Enmark, E, Gustafsson, J-Å & Nilsson, S (1998) Differential response of estrogen receptor α and estrogen receptor β to partial estrogen agonists/antagonists. Molecular Pharmacology 54, 105112.CrossRefGoogle ScholarPubMed
Bar-Tana, J (2001) Peroxisome proliferator-activated receptor gamma (PPARγ) activation and its consequences in humans. Toxicology Letters 120, 919.CrossRefGoogle ScholarPubMed
Bernstein, L & Press, MF (1998) Does estrogen receptor expression in normal breast tissue predict breast cancer risk? Journal of the National Cancer Institute 90, 57.Google Scholar
Bingham, SA, Atkinson, C, Liggins, J, Bluck, L & Coward, A (1998) Phyto-oestrogens: where are we now? British Journal of Nutrition 79, 393406.CrossRefGoogle ScholarPubMed
Birnbaum, LS (2000) Health effects of dioxins: people are animals and vice versa!. Organohalogen Compounds 49, 101103.Google Scholar
Blumberg, B & Evans, RM (1998) Orphan nuclear receptors – new ligands and new possibilities. Genes and Development 12, 31493155.CrossRefGoogle ScholarPubMed
Blumberg, B, Sabbagh, W, Juguilon, H, Bolado, J, Van Meter, CM, Ong, ES & Evans, RM (1998) SXR, a novel steroid and xenobiotic sensing nuclear receptor. Genes and Development 12, 31953205.CrossRefGoogle ScholarPubMed
Boettger-Tong, H, Murthy, L, Chiappetta, C, Kirkland, JL, Goodwin, B, Adlercreutz, H, Stancel, GM & Makela, S (1998) A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens. Environmental Health Perspectives 106, 369373.Google Scholar
Bradbury, RB & White, DE (1954) Estrogens and related substances in plants. Vitamins and Hormones 12, 207233.CrossRefGoogle ScholarPubMed
Bradlow, HL, Davis, DL, Lin, G, Sepovic, D & Tiwari, R (1995) Effects of pesticides on the ratio of 16 alphahydroxyestrone/ 2hydroxyestrone: a biologic marker of breast cancer risk. Environmental Health Perspectives 103, 147150.Google Scholar
Bradlow, HL, Davis, D, Sepkovic, DW, Tiwari, R & Osbourne, MP (1997) Role of the estrogen receptor in the action of organochlorine pesticides on estrogen metabolism in human breast cancer cell lines. Science of the Total Environment 208, 914.CrossRefGoogle ScholarPubMed
Brodie, A, Lu, Q & Long, B (1999) Aromatase and its inhibitors. Journal of Steroid Biochemistry and Molecular Biology 69, 205210.CrossRefGoogle ScholarPubMed
Brzozowski, AM, Pike, AC, Dauter, Z, Hubbard, RE, Bonn, T, Engstrom, O, Ohman, L, Greene, GL, Gustafsson, J-Å & Carlquist, M (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753758.CrossRefGoogle ScholarPubMed
Burbach, KM, Poland, A & Bradfield, CA (1992) Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proceedings of the National Academy of Sciences USA 89, 815819.CrossRefGoogle ScholarPubMed
Burow, ME, Tang, Y, Collins-Burow, BM, Krajewski, S, Reed, JC, McLachlan, JA & Beckman, BS (1999) Effects of environmental estrogens on tumor necrosis factor α-mediated apoptosis in MCF-7 cells. Carcinogenesis 20, 20572061.CrossRefGoogle ScholarPubMed
Cassidy, A (1996) Physiological effects of phyto-oestrogens in relation to cancer and other human health risks. Proceedings of the Nutrition Society 55, 399417.CrossRefGoogle ScholarPubMed
Cassidy, A & Faughnan, M (2000) Phyto-oestrogens through the life cycle. Proceedings of the Nutrition Society 59, 489496.CrossRefGoogle ScholarPubMed
Cassidy, A & Milligan, S (1998) How significant are environmental oestrogens to women? Climeractic 1, 229242.CrossRefGoogle ScholarPubMed
Choi, H-S, Chung, M, Tzameli, I, Simha, D, Lee, Y-K, Seol, W & Moore, DD (1997) Differential transactivation by two isoforms of the orphan nuclear hormone receptor CAR. Journal of Biological Chemistry 272, 2356523571.CrossRefGoogle ScholarPubMed
Colburn, T, Dumanoski, D & Myers, JP (1999) Our Stolen Future: Are We Threatening Our Fertility, Intelligence, and Survival? – A Scientific Detective Story. New York: Dutton.Google Scholar
Colburn, T, Vom Saal, FS & Soto, AM (1993) Developmental effects of endocrine disrupting chemicals in wildlife and humans. Environmental Health Perspectives 101, 378384.CrossRefGoogle Scholar
Collett, GP, Betts, AM, Johnson, MI, Pulimood, AB, Cook, S, Neal, DE & Robson, CN (2000) Peroxisome proliferator-activated receptor α is an androgen responsive gene in human prostate and is highly expressed in prostatic adenocarcinoma. Clinical Cancer Research 6, 32413248.Google Scholar
Crain, DA, Rooney, AA, Orlando, EF & Guillette, LJ Jr (2000) Endocrine disrupting contaminants and hormone dynamics: Lessons from wildlife. In Environmental Endocrine Disruptors, an Evolutionary Perspective, pp. 121[Guillette, L Jr and Crain, DA, editors\. New York: Taylor & Francis.CrossRefGoogle Scholar
Davidson, NE & Yager, JD (1997) Pesticides and breast cancer: Fact or fad? Journal of the National Cancer Institute 89, 17431744.CrossRefGoogle ScholarPubMed
Davis, DL, Bradlow, HL, Wolff, M, Woodruff, T, Hoel, DG & Anton-Culver, H (1993) Medical hypothesis: Xenoestrogens as preventable causes of breast cancer. Environmental Health Perspectives 101, 372377.CrossRefGoogle ScholarPubMed
Davis, DL, Telang, NT, Osborne, MP & Bradlow, HL (1997) Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer. Environmental Health Perspectives 105, 571576.Google ScholarPubMed
Diliberto, JJ, Abbot, BD & Birnbaum, LS (2000) Use of AhR knockout (AhR-/-) mice to investigate the role of the Ah receptor on the disposition of TCDD. Organohalogen Compounds 49, 121123.Google Scholar
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. Clinical Cancer Research 8, 21032107.Google Scholar
Ebling, FJP, Brooks, AN, Cronin, AS, Ford, H & Kerr, JB (2000) Estrogenic induction of spermatogenesis in the hypogonadal mouse. Endocrinology 141, 28612869.CrossRefGoogle ScholarPubMed
Falck, F Jr, Ricci, A Jr, Wolff, MS, Godbold, J & Deckers, P (1992) Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Archives of Environmental Health 47, 143146.Google ScholarPubMed
Food and Agriculture Organization/World Health Organization (1998 a). Residues of Some Veterinary Drugs in Animals and Foods. FAO Food and Nutrition Paper no. 41. Rome: FAO.Google Scholar
Food and Agriculture Organization/World Health Organization (1988 b). Evaluation of Certain Veterinary Drugs Residues in Food. WHO Technical Report Series no. 763. Geneva: WHO.Google Scholar
Forman, BM, Tzameli, I, Choi, H-S, Chen, J, Simha, D, Seol, W, Evans, RM & Moore, DD (1998) Androstane metabolites bind to and deactivate the nuclear receptor CAR-β. Nature 395, 612615.CrossRefGoogle ScholarPubMed
Franks, S, Gharani, N & Gilling-Smith, C (1999) Polycystic ovary syndrome: evidence for a primary disorder of ovarian steroidogenesis. Journal of Steroid Biochemistry and Molecular Biology 69, 269272.CrossRefGoogle ScholarPubMed
Fujimoto, J, Hirose, R, Sakaguchi, H & Tamaya, T (2000) Clinical significance of expression of estrogen receptor alpha and beta mRNA in ovarian cancers. Oncology 58, 334341.CrossRefGoogle ScholarPubMed
Fuqua, SAW, Wiltschke, C, Zhang, QX, Borg, Å, Castles, CG, Friedrichs, WE, Hopp, T, Hilsenbeck, S, Mohsin, S, O'Connell, P & Allred, DC (2000) A hypersensitive estrogen receptor alpha mutation in premalignant breast lesions. Cancer Research 60, 40264029.Google ScholarPubMed
Gaido, KW, Leonard, LS, Maness, SC, Hall, JM, McDonnell, DP, Saville, B & Safe, S (1999) Differential interaction of the methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-tricloroethane with estrogen receptors α and β. Endocrinology 140, 57465753.CrossRefGoogle Scholar
Gillner, M, Bergman, J, Ambilleau, C, Feruström, B & Gustafsson, J-Å (1993) Interactions of indolo [3–2–6]carbazoles and related polycyclic aroma hydrocarbons with specific binding sites for 2,3,7,8-tetrachlorodobenzo-p-dioxin in rat liver. Molecular Pharmacology 28, 336345.Google Scholar
Giwercman, A, Carlsen, E, Keiding, N & Skakkebaek, NE (1993) Evidence for the increasing incidence of abnormalities of the human testis: A review. Environmental Health Perspectives 102, Suppl., 6571.Google Scholar
Gray, EL, Kelce, WR, Wiese, T, Tyl, R, Gaido, K & Cook, J (1997) Endocrine screening methods workshop report: detection of estrogenic and androgenic hormonal and antihormonal activity for chemicals that act via receptor or steroidogenic enzyme mechanisms. Reproductive Toxicology 11, 719750.Google Scholar
Guillette, LJ & McLachlan, JA (1996) Ecosystems and embryos – is there a scientific basis for concern? Animal Reproduction Science 42, 1324.CrossRefGoogle Scholar
Gustafsson J-Å, (1999) Estrogen receptor β – a new dimension in estrogen mechanism of action. Journal of Endocrinology 163, 379383.Google Scholar
Gustaffson, J-Å (2000) The role of the ERβ in oestrogen mediated carcinogenesis. Toxicology Letters 116, 1.Google Scholar
Hahn, ME (1998) The aryl hydrocarbon receptor: a comparative perspective. Comparative Biochemistry and Physiology 121C, 2353.Google Scholar
Hall, JM & McDonnell, DP (1999) The estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ER α transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140, 55665578.CrossRefGoogle ScholarPubMed
Heath-Pagliuso, S, Rogers, WJ, Tullis, K, Seidel, SD, Cenijin, PH, Brouwer, A & Denison, MS (1998) Activation of the Ah receptor by tryptophan and tryptophan metabolites. Biochemistry 37, 1150811515.CrossRefGoogle Scholar
Hess, RA, Bunick, D, Lee, K-H, Bahr, J, Taylor, JA, Korach, KS & Lubahn, DB (1997) A role for oestrogens in the male reproductive system. Nature 390, 509512.CrossRefGoogle ScholarPubMed
Hillman, GG, Forman, JD, Kucuk, O, Yudelev, M, Maughan, RL, Rubio, J, Layer, A, Tekyi-Mensah, S, Abrams, J & Sarkar, FH (2001) Genistein potentiates the radiation effect on prostrate carcinoma cells. Clinical Cancer Research 7, 382390.Google Scholar
Honkakoski, P, Zelko, I, Sueyoshi, T & Negishi, M (1998) The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer nodule of the CYP2B gene. Molecular and Cellular Biology 18, 56525658.Google Scholar
Howdeshell, KL, Hotchkiss, AK, Thayer, KA, Vandenbergh, JG & vom Saal, FS (1999) Exposure to bisphenol α advances puberty. Nature 401, 763765.CrossRefGoogle Scholar
Hunter, DJ, Hankinson, SE, Laden, F, Colditz, GA, Manson, JE, Willet, WC, Speizer, FE & Wolff, MS (1997) Plasma organochlorine levels and the risk of breast cancer. New England Journal of Medicine 337, 12531258.CrossRefGoogle ScholarPubMed
Hunter, DJ & Kelsey, KT (1993) Pesticide residues and breast cancer. The harvest of a silent spring. Journal of the National Cancer Institute 85, 598599.Google Scholar
Jacobs, MN (1998) Molecular modelling of oestrogenic compounds in the human oestrogen receptor and investigation of the activity of oestrogenic compounds in breast cancer cell lines. MSc Thesis, University of Surrey.Google Scholar
Jacobs, MN, Covaci, A & Schepens, P (2001 a) Investigation of polybrominated diphenyl ether in Scottish and European farmed atlantic salmon (Salmo salar), salmon aquaculture feed and fish oils. Organohalogen Compounds 51, 239242.Google Scholar
Jacobs, MN, Covaci, A, Schepens, P & Millstone, E (2001 b) Investigation of selected PCBs and organochlorine pesticides in farmed atlantic salmon (Salmo salar), salmon aquaculture feed and fish oil components of the feed. Organohalogen Compounds 51, 314318.Google Scholar
Jacobs, MN, Ferrario, J & Byrne, C (2000) Investigation of PCDDs, PCDFs and selected coplanar PCBs in Scottish farmed Atlantic salmon. Organohalogen Compounds 47, 338341.Google Scholar
Jacobs, MN & Lewis, DFV (1999) A QSAR study of organochlorine and isoflavonoid compounds ligand binding affinity to the human oestrogen receptor α. Organohalogen Compounds 41, 517520.Google Scholar
Jacobs, MN & Lewis, DFV (2000) Homology modelling of the human peroxisome proliferator activated receptorα (PPARα) ligand binding domain from the human PPARγ crystal structure. Toxicology Letters 116, Suppl. 1, 59.Google Scholar
Jacobs, MN, Starkey, S & Hoffman, R (1999) Combination effects of different ratios of PCB 153 and the phytoestrogen genistein upon DNA synthesis in an MCF-7 breast cancer cell line. Organohalogen Compounds 42, 7377.Google Scholar
Johnson, TE, Holloway, MK, Vogel, R, Rutledge, SJ, Perkins, JJ, Rodan, GA & Scmidt, A (1997) Structural requirements and cell type specifity for ligand activation of peroxisome proliferator activated receptors. Journal of Steroid Biochemistry and Molecular Biology 63, 18.Google Scholar
Jones, SA, Moore, LB, Shenk, JL, Wisley, GB, Hamilton, GA, McKee, DD, Tomkinson, NCO, LeCluyse, EL, Lambert, MH, Willson, TM, Kliewer, SA & Moore, JT (2000) The pregnane X receptor: A promiscuous xenobiotic receptor that has diverged during evolution. Molecular Endocrinology 14, 2739.CrossRefGoogle ScholarPubMed
Kelce, RW, Stone, RC, Laws, CS, Gray, EL, Kemppainen, AJ & Wilson, ME (1995) Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature 373, 581585.Google Scholar
Kelley, ST & Thackray, VG (1999) Phylogenetic analyses reveal ancient duplication of estrogen receptor isoforms. Journal of Molecular Evolution 49, 609614.Google Scholar
Klein, KO, Baron, J, Colli, MJ, McDonnell, DP & Cutler, GB Jr (1994) Estrogen levels in childhood determined by ultrasensitive recombinant cell bioassay. Journal of Clinical Investigation 94, 24752480.Google Scholar
Kliewer, SA, Lehmann, JM & Willson, TM (1999) Orphan nuclear receptors: Shifting endocrinology into reverse. Science 284, 757760.Google Scholar
Kliewer, SA, Moore, JT, Wade, L, Staudinger, JL, Watson, MA, Jones, SA, McKee, DD, Oliver, BB, Willson, TM, Zetterström, RH, Perlmann, T & Lehmann, JM (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92, 7382.Google Scholar
Kreiger, N, Wolff, MS, Hiatt, RA, Rivera, M, Vogelman, J & Orentreich, N (1994) Breast cancer and serum organochlorines: a prospective study among white, black and Asian women. Journal of the National Cancer Institute 86, 589599.Google Scholar
Krstevska-Konstantinova, M, Charlier, C, Craen, M, Du Caju, M, Heinrichs, C, de Beaufort, C, Plomteux, G & Bourguignon, JP (2001) Sexual precocity after immigration from developing countries to Belgium: evidence of previous exposure to organochlorine pesticides. Human Reproduction 16, 10201020.Google Scholar
Kuiper, GCJM, Carlsson, B, Grandien, K, Enmark, E, Haggblad, J, Nilsson, S & Gustafsson, J-Å (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138, 863870.CrossRefGoogle ScholarPubMed
Kuiper, GCJM, Lemmen, JG, Carlsson, B, Corton, JC, Safe, SH, van der Saag, PT, van der Burg, B & Gustafsson, J-Å (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor ß. Endocrinology 139, 42524263.CrossRefGoogle Scholar
Lamartinière, CA, Moore, J, Holland, MB & Barnes, S (1995) Neonatal genistein chemoprevents mammary carcinogenesis. Proceedings of the Society of Experimental Biology and Medicine 208, 120123.Google Scholar
Lau, K-M, LaSpina, M, Long, J & Ho, S-M (2000) Expression of estrogen receptor (ER) ER-β in normal and malignant prostatic epithelial cells: regulation by methylation and involvement of growth regulation. Cancer Research 60, 31753182.Google ScholarPubMed
Lau, K-M, Mok, SC & Ho, S-M (1999) Expression of human estrogen receptor α and β, progesterone receptor and androgen receptor mRNA in normal and malignant ovarian epithelial cells. Proceedings of the National Academy of Sciences USA 96, 57225727.Google Scholar
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. Journal of Clinical Investigation 102, 10161023.Google Scholar
Lewis, DFV & Jacobs, MN (1999) A QSAR study of some PCBs ligand-binding affinity to the cytosolic Ah receptor. Organohalogen Compounds 41, 537540.Google Scholar
Lewis, DFV & Lake, B (1998) Molecular modelling of the rat peroxisome proliferator-activated receptor α (rPPARα) by homology with the human retinoic acid X receptor α (hRARα) and investigation of peroxisome proliferator binding interactions: QSARs. Toxicology In Vitro 12, 619632.Google Scholar
Liem, AKD, Fürst, P & Rappe, C (2000) Exposure of populations to dioxins and related compounds. Food Additives and Contaminants 17, 241259.CrossRefGoogle ScholarPubMed
Luo, X, Ikeda, Y, Lala, D, Rice, D, Wong, M & Parker, KL (1999) Steroidogenic factor-1 (SF-1) is essential for endocrine development and function. Journal of Steroid Biochemistry and Molecular Biology 69, 1318.Google Scholar
McLachlan, JA (1997) Synergistic effect of environmental oestrogens: report withdrawn. Science 277, 463464.CrossRefGoogle ScholarPubMed
McLachlan, JA Burow, M, Chiang, T-C, & Fang Li, S (2001) Gene imprinting in developmental toxicology: a possible interface between physiology and pathology. Toxicology Letters 120, 161164.Google Scholar
Martucci, CP & Fishman, J (1993) P450 enzymes of estrogen metabolism. Pharmacology Therapy 57, 237257.Google Scholar
Masahiko, N & Honkakoski, P (2000) Induction of drug metabolism by nuclear receptor CAR: molecular mechanisms and implications for drug research. European Journal of Pharmacological Sciences 11, 259264.CrossRefGoogle ScholarPubMed
Masuyama, H, Hiramatsu, Y, Kunitomi, M, Kudo, T & MacDonald, PN (2000) Endocrine disrupting chemicals, phthalic acid and nonylphenol, activate pregnane X receptor-mediated transcription. Molecular Endocrinology 14, 421428.Google Scholar
Matthews, JB, Twomey, K & Zacharewski, TR (2001) In vitro and in vivo interactions of bisphenol A and its metabolite, bisphenol A glucuronide, with estrogen receptors α and β. Chemical Research in Toxicology 14, 149157.Google Scholar
Maurel, P (1996) The CYP3A family . In Cytochromes P450: Metabolic and Toxicological Aspects, pp. 241270[Ionnides, C, editor]. Boca Raton, FL: CRC Press Inc.Google Scholar
Meerts, IATM, Letcher, RJ, Hoving, S, Marsh, G, Bergman, Å, Lemmen, JG, van der Berg, B & Brouwer, A (2001) In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PBDEs and polybrominated bisphenol A compounds. Environmental Health Perspectives 109, 399407.Google Scholar
Memon, RA, Tecott, LH, Nonogaki, K, Beigneux, A, Moser, AH, Grunfeld, C & Feingold, KR (2000) Up-regulation of peroxisome proliferator-activated receptor α (PPARα) and PPARγ messenger ribonucleic acid expression in the liver in murine obesity: Troglitazone induces expression of PPARγ responsive adipose tissue-specific genes in the liver of obese diabetic mice. Endocrinology 141, 40214031.Google Scholar
Milligan, SR, Balasubramanian, AV & Kalita, JC (1998) Relative potency of xenobiotic estrogens in an acute in vivo mammalian assay. Environmental Health Perspectives 106, 2326.CrossRefGoogle Scholar
Milligan, SR, Kalita, JS, Heyerick, A, Rong, H, De Coomsan, L & De Keukeleire, D (1999) Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. Journal of Clinical Endocrinology and Metabolism 84, 22492252.Google Scholar
Miyamoto, T, Keneko, A, Kakizawa, T, Yajima, H, Kamijo, K, Sekine, R, Hiramatsu, K, Nishii, Y, Hashimoto, T & Hashizume, K (1997) Inhibition of peroxisome proliferator signaling pathways by thyroid hormone recepter – competitive binding to the response element. Journal of Biological Chemistry 272, 77527758.CrossRefGoogle Scholar
Moore, LB, Goodwin, B, Jones, SA, Wisely, GB, Willson, TM, Collins, JL & Kliewer, SA (2000) St. John's Wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences USA 97, 75007502.Google Scholar
Mosselman, S, Polman, J & Dijkema, R (1996) ER beta: Identification and characterization of a novel human estrogen receptor. FEBS Letters 392, 4953.CrossRefGoogle ScholarPubMed
Mueller, E, Sarraf, P, Tontonoz, P, Evans, RM, Martin, KJ, Zhang, M, Fletcher, C, Singer, S & Spiegelman, BM (1998) Terminal differentiation of human breast cancer through PPAR gamma. Molecular Cell 1, 465470.Google Scholar
National Institute of Environmental Health Sciences, National Institutes of Health (2001) National Toxicology Program's Report of the endocrine disruptors low-dose peer review. http://ntp-server.niehs.nih.gov/htdocs/liason/LowDosePeerFinalRpt.pdf.Google Scholar
Nelson, KG, Sakai, Y, Eitzman, B, Steed, T & McLachlan, JA (1994) Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen regulated genes. Cell Growth and Differentiation 5, 595606.Google Scholar
Nelson, KG, Takahashi, T, Bossert, NL, Walmer, DK & McLachlan, JA (1991) Epidermal growth factor replaces estrogen in the stimulation of female genital tract growth and differentiation. Proceedings of the National Academy of Sciences USA 88, 2125.Google Scholar
Newbold, RR, Padilla Banks, E, Bullock, B & Jefferson, WN (2001) Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Research 61, 43254328.Google ScholarPubMed
Nguyen, TA, Hoivik, D, Lee, J-E, & Safe, S (1999) Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex. Archives of Biochemistry and Biophysics 367, 250257.Google Scholar
Nolte, RT, Wisely, GB, Westin, S, Cobb, JE, Lambert, MH, Kurokawa, R, Rosenfeld, MG, Willson, TM, Glass, CK & Milburn, MV (1998) Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 395, 137143.Google Scholar
Ogawa, S, Chan, J, Chester, AE, Gustafsson, J-A, Korach, KS & Pfaff, DW (1999) Survival of reproductive behaviours in estrogen receptor beta gene-deficient (βERKO) male and female mice. Proceedings of the National Academy of Science USA 96, 1288712892.Google Scholar
Paech, K, Webb, P, Kuiper, GGJM, Nilsson, S, Gustafsson, J-Å, Kushner, PJ & Scanlan, TS (1997) Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science 277, 15081510.Google Scholar
Parker, MG (1993) Steroid and related receptors. Current Opinion in Cell Biology 5, 499504.Google Scholar
Pascussi, J-M, Jounaidi, Y, Drocourt, L, Domergue, J, Balabaud, C, Maurel, P & Vilarem, M-J (1999) Evidence for the presence of a functional pregnane X receptor response element in the CYP3A7 promoter gene. Biochemical and Biophysical Research Communications 260, 377381.Google Scholar
Payne, J, Scholze, M & Kortenkamp, A (2001) Mixtures of four organochlorines enhance human breast cancer cell proliferation. Environmental Health Perspectives 109, 391397.Google Scholar
Petersen, DN, Tkalcevic, GT, Koza-Taylor, PH, Turi, TG & Brown, TA (1998) Identification of estrogen receptor beta (2), a functional variant of estrogen receptor beta expressed in normal rat tissues. Endocrinology 139, 10821092.CrossRefGoogle ScholarPubMed
Petreas, M, She, J, Winkler, P, McKinney, M, Reynolds, P, Smith, D, Gilliss, D, Hurley, S, Jeffrey, S & Mahoney, ME (1998) Levels of PCDD/PCDFs, PCBs and OC pesticides in breast adipose tissue of women enrolled in a California breast cancer study. Organohalogen Compounds 38, 3740.Google Scholar
Phelan, D, Winter, GM, Rogers, WJ, Lam, JC & Dennison, MS (1998) Activation of the Ah Receptor signal transduction pathway by bilrubin and biliverdin. Archives of Biochemistry and Biophysics 357, 155163.Google Scholar
Poellinger, L (2000) Mechanistic aspects – the dioxin (aryl hydrocarbon) receptor. Food Additives and Contaminants 17, 261266.CrossRefGoogle ScholarPubMed
Porta, M, Malats, N, Jariod, M, Grimault, JO, Rifà, J, Carrato, A, Guarner, L, Salas, A, Santiago-Silva, M, Corominas, JM, Andreu, M & Real, FX (1999) Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer. Lancet 354, 21252129.Google Scholar
Ramamoorthy, K, Wang, K, Chen, I-C, Safe, S, Norris, JD, McDonnell, DP, Gaido, KW, Bocchinfuso, WP & Korach, KS (1997) Potency of combined estrogenic pesticides. Science 275, 405406.Google Scholar
Ross, JL, Cassorla, FG, Skerda, MC, Valk, IM, Loriaux, DL & Cutler, GB (1983) A preliminary study of the effect of estrogen dose on growth in Turner's syndrome. New England Journal of Medicine 309, 11041106.Google Scholar
Ross, JL, Long, LM, Skerda, MC, Cassorla, FG, Kurtz, D, Loriaux, DL & Cutler, GB (1986) Effects of low doses of estradiol on 6-month growth rates and predicted height in patients with Turner syndrome. Journal of Pediatrics 109, 150953.Google Scholar
Rubin, GL, Zhao, Y, Kalus, AM & Simpson, ER (2000) Peroxisome proliferator-activated receptor γ ligands inhibit estrogen bio-synthesis in human breast tissue: possible implications for breast cancer therapy. Cancer Research 60, 16041608.Google Scholar
Safe, S (1997) Xenoestrogens and breast cancer. New England Journal of Medicine 337, 13031304.Google Scholar
Safe, S, Connor, K, Ramamoorthy, K, Gaido, K & Maness, S (1997) Human exposure to endocrine-active chemicals: hazard assessment problems. Regulatory Toxicology and Pharmacology 26, 5258.CrossRefGoogle ScholarPubMed
Safe, SH (1995) Environmental and dietary estrogens and human health: is there a problem? Environmental Health Perspectives 103, 346351.Google Scholar
Scheutz, 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. Molecular Pharmacology 54, 11131117.Google Scholar
Sharpe, RM (1997) Do males rely on female hormones? Nature 390, 447448.CrossRefGoogle ScholarPubMed
Sharpe, RM (2001) Hormones and testis development and the possible adverse effects of environmental chemicals. Toxicology Letters 120, 221232.CrossRefGoogle ScholarPubMed
Sharpe, RM, Atanassova, N, McKinnell, C, Parte, P, Turner, KJ, Fisher, JS, Kerr, JB, Groome, NP, Macpherson, S, Millar, MR & Saunders, PTK (1998) Abnormalities in functional development of the Sertoli cells in rats treated neonatally with diethylstilbestrol: A possible role for estrogens in Sertoli cell development. Biology of Reproduction 59, 10841094.Google Scholar
Sharpe, RM & Skakkebæk, NE (1993) Are oestrogens involved in falling sperm counts and disorders of the reproductive tract? Lancet 341, 13921395.Google Scholar
Sheeler, CQ, Dudley, MW & Khan, SA (2000) Environmental estrogens induce transcriptionally active estrogen receptor dimers in yeast: Activity potentiated by the coactivator RIP140. Environmental Health Perspectives 108, 97103.Google Scholar
Shen, K & Novak, RF (1997 a) Differential effects of aroclors and DDT on growth factor gene expression and receptor tyrosine kinase activity in human breast epithelial cells. Advances in Experimental Medicine and Biology 407, 295302.Google Scholar
Shen, K & Novak, RF (1997 b) DDT stimulates c-erbB2, c-met, and STATS tyrosine phosphorylation, Grb2-sos association, MAPK phosphorylation, and proliferation of human breast epithelial cells. Biochemical and Biophysical Research Communications 231, 1721.Google Scholar
Sher, T, Yi, H-F, McBride, OW & Gonzalez, FJ (1993) cDNA-cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 32, 55985604.Google Scholar
Shughrue, PJ & Merchenthaler, I (2000) Estrogen is more than just a sex hormone: Novel sites for estrogen action in the hippocampus and cerebral cortex. Frontiers in Neuroendocrinology 21, 95101.Google Scholar
Simpson, ER, Rubin, G, Clyne, C, Robertson, K, O'Donnell, L, Jones, M & Davis, S (2000) The role of local estrogen biosynthesis in males and females. Trends in Environmental Medicine 11, 184188.Google Scholar
Sinal, CJ & Bend, RJ (1997) Aryl hydrocarbon receptor-dependent induction of Cyplal by bilirubin in mouse hepatatoma hepa 1c1c7 cells. Molecular Pharmacology 52, 590599.Google Scholar
Soto, AM, Sonnenschein, C, Chung, KL, Fernandez, MF, Olea, N & Serrano, FO (1995) The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environmental Health Perspectives 103, 113122.Google Scholar
Stevens, JT, Breckenridge, CB, Wetzel, LT, Gillis, JH, Luempert, LG & Eldridge, LC (1994) Hypothesis for mammary tumourigenesis in Sprague-Dawley rats exposed to certain triazine herbicides. Journal of Toxicology and Environmental Health 43, 139153.Google Scholar
Tetsuka, M, Anderson, RA & Hillier, SG (1997) Distribution of messenger RNA's encoding oestrogen receptor isoforms in female reproductive tissues. Journal of Endocrinology 152, OC20.Google Scholar
Tielemans, E, Van Kooij, R, Te Velde, ER, Burdoff, A & Heederik, D (1999) Pesticide exposure and decreased fertilisation rates in vitro. Lancet 354, 484485.Google Scholar
Uauy, R, Mena, P & Rojas, C (2000) Essential fatty acids in early life: structural and functional role. Proceedings of the Nutrition Society 59, 315.Google Scholar
United Nations Environment Programme (2001) The Stockholm Convention on Persistent Organic Pollutants. http://www.chem. unep.ch/pops/Google Scholar
US Environmental Protection Agency (2001) Endocrine disrupter screening program. http://www.epa.gov/scipoly/oscpendo/ index.htmGoogle Scholar
US Food and Drug Administration (1999)Guideline 3, part 2: Guideline for toxicological testing. http://www.fda.gov/dms/ pestpts.htmlGoogle Scholar
Warner, M, Nilsson, S & Gustafsson, J-Å (1999) The estrogen receptor family. Current Opinion in Obstetrics and Gynecology 11, 249254.Google Scholar
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, 23292333.Google Scholar
Waxman, DJ (1999) P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Archives of Biochemistry and Biophysics 369, 1123.CrossRefGoogle ScholarPubMed
Weigel, N (1996) Steroid hormone receptors and their regulation by phosphorylation. Biochemical Journal 319, 657667.CrossRefGoogle ScholarPubMed
Whitten, PL & Patisaul, HB (2001) Cross species and interassay comparisons of phytoestrogen action. Environmental Health Perspectives 109, 517.Google Scholar
Willson, TM, Brown, PJ, Sternbach, DD & Henke, BR (2000) The PPARs: from orphan receptors to drug discovery. Journal of Medicinal Chemistry 43, 527550.CrossRefGoogle ScholarPubMed
Wise, PM, Dubal, DB, Wilson, ME, Rau, SW & Böttner, M (2001) Minireview: Neuroprotective effects of oestrogen – New insights into mechanisms of action. Endocrinology 142, 969973.CrossRefGoogle ScholarPubMed
Wolff, MS & Toniolo, PG (1995) Environmental organochlorine exposure and potential etiologic factor in breast cancer. Environmental Health Perspectives 103, 141145.Google Scholar
Wolff, MS, Toniolo, PG, Lee, EW, Rivera, M & Dubin, N (1993) Blood levels of organochlorine residues and risk of breast cancer. Journal of the National Cancer Institute 85, 648652.CrossRefGoogle ScholarPubMed
Xie, W, Barwick, JL, Simon, CM, Pierce, AM, Safe, S, Blumberg, B, Guzelian, PS & Evans, RE (2000) Reciprocal activation of xenobiotic response genes by nuclear receptors SXR/PXR and CAR. Genes and Development 14, 30143023.CrossRefGoogle ScholarPubMed
Xu, HE, Lambert, MH, Montana, VG, Plunket, KD, Moore, LB, Collins, JL, Oplinger, JA, Kliewer, SA, Gampe, RT Jr, McKee, DD, Moore, JT & Willson, TM (2001) Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Procedings of the National Academy of Sciences USA 98, 1391913924.Google Scholar
Zhou, J-R & Lee, AS (1998) Mechanism for the suppression of the mammalian stress response by genistein, an anticancer phytoestrogen from soy. Journal of the National Cancer Institute 90, 381388.Google Scholar
Zomer, AWM, van den Berg, B, Jansen, GA, Wanders, RJA, Tien Poll-The, B & van der Saag, PT (2000) Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator activated receptorα Journal of Lipid Research 41, 18011807.Google Scholar