Analytical and Bioanalytical Chemistry

, Volume 378, Issue 3, pp 582–587

Xenoestrogens: mechanisms of action and detection methods

Review

Abstract

Estrogenic compounds exert pleiotropic effects in wildlife and humans, and endogenous estrogens, like 17β-estradiol, regulate growth and development of their target tissues. Environmental, industrial, or naturally occurring chemicals that possess estrogenic and/or antiestrogenic activities are termed xenoestrogens and may interfere with endocrine systems. These xenoestrogens are therefore defined as endocrine-active or endocrine-disrupting compounds. The estrogen receptor (ER) is the major regulatory unit within the estrogen-signaling pathway and the molecular mechanisms of estrogen and ER actions are described briefly. Based on the mechanism of ER action, in vitro test systems are described that can be employed for screening but also for the elucidation of mechanisms of action of (anti)estrogenic compounds. How screening assays and mechanistic studies can aid in human risk assessment for potential endocrine-active compounds is discussed also.

Keywords

Estrogen receptor ERα ERβ Endocrine-active compound Endocrine disruptor 

References

  1. 1.
    Colburn T, Clement C (1992) Chemically induced alterations in sexual and functional development: the wildlife/human connection. Princeton Scientific Publishing, PrincetonGoogle Scholar
  2. 2.
    Newbold RR, McLachlan JA (1996) Transplacental hormonal carcinogenesis: diethylstilbestrol as an example. In: Huff J, Boyd J, Barrett JC (eds) Cellular and molecular mechanisms of hormonal carcinogenesis: environmental influences. Wiley-Liss, New York, pp 131–147Google Scholar
  3. 3.
    Tsai M-J, O’Malley B (1994) Annu Rev Biochem 63:451–486PubMedGoogle Scholar
  4. 4.
    Gray JLE, Ostby J, Wilson V, Lambright C, Bobseine K, Hartig P, Hotchkiss A, Wolf C, Furr J (2002) Toxicology 181–182:371–382Google Scholar
  5. 5.
    Gray LE Jr, Kelce WR, Wiese T, Tyl R, Gaido K, Cook J, Klinefelter G, Desaulniers D, Wilson E, Zacharewski T, Waller C, Foster P, Laskey J, Reel J, Giesy J, Laws S, McLachlan J, Breslin W, Cooper R, Di Giulio R, Johnson R, Purdy R, Mihaich E, Safe S, Colborn T (1997) Reprod Toxicol 11:719–750CrossRefPubMedGoogle Scholar
  6. 6.
    Ashby J (2000) Toxicol Pathol 28:432–437PubMedGoogle Scholar
  7. 7.
    Mueller SO (2002) J Chromatogr B 777:155–165CrossRefGoogle Scholar
  8. 8.
    Safe S, Wang F, Porter W, Duan R, McDougal A (1998) Toxicol Lett 102–103:343–347Google Scholar
  9. 9.
    Evans RM (1988) Science 240:889–895PubMedGoogle Scholar
  10. 10.
    Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schuetz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) Cell 83:835–839PubMedGoogle Scholar
  11. 11.
    Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P (1986) Nature 320:134–139PubMedGoogle Scholar
  12. 12.
    Green S, Walter P, Greene G, Krust A, Goffin C, Jensen E, Scrace G, Waterfield M, Chambon P (1986) J Steroid Biochem 24:77–83CrossRefPubMedGoogle Scholar
  13. 13.
    Kuiper GGJM, Enmark E, Pelto-Huiko M, Nilsson S, Gustafsson J (1996) Proc Natl Acad Sci USA 93:5925–5930PubMedGoogle Scholar
  14. 14.
    Mosselman S, Polman J, Dijkema R (1996) FEBS Lett 392:49–53CrossRefPubMedGoogle Scholar
  15. 15.
    Couse JF, Korach KS (1999) Endocrine Rev 20:358–417Google Scholar
  16. 16.
    Couse JF, Hewitt SC, Bunch DO, Sar M, Walker VR, Davis BJ, Korach KS (1999) Science 286:2328–2331CrossRefPubMedGoogle Scholar
  17. 17.
    Mueller SO, Korach KS (2001) Curr Opin Pharmacol 1:613–619CrossRefPubMedGoogle Scholar
  18. 18.
    Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies, O (1998) Proc Natl Acad Sci USA 95:15677–15682CrossRefPubMedGoogle Scholar
  19. 19.
    Couse JF, Bunch DO, Lindzey J, Schomberg DW, Korach KS (1999) Endocrinology 140:5855–5865PubMedGoogle Scholar
  20. 20.
    Prins GS, Birch L, Couse JF, Cho, I, Katzenellenbogen B, Korach KS (2001) Cancer Res 61:6089–6097PubMedGoogle Scholar
  21. 21.
    Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA (1998) Endocrinology 139:4252–4263PubMedGoogle Scholar
  22. 22.
    Liu MM, Albanese C, Anderson CM, Hilty K, Webb P, Uht RM, Price RH, Pestell RG, Kushner PJ (2002) J Biol Chem 277:24353–24360CrossRefPubMedGoogle Scholar
  23. 23.
    Weihua Z, Lathe R, Warner M, Gustafsson JA (2002) Proc Natl Acad Sci USA 99:13589–13594CrossRefPubMedGoogle Scholar
  24. 24.
    Hall JM, Couse JF, Korach KS (2001) J Biol Chem 276:36869–36872CrossRefPubMedGoogle Scholar
  25. 25.
    Mueller SO, Korach KS (2001) Mechanisms of estrogen receptor-mediated agonistic and antagonistic effects. In: Metzler M (ed) Endocrine disruptors. Springer, Berlin Heidelberg New York, pp 1–25Google Scholar
  26. 26.
    Hyder SM, Chiappetta C, Stance, GM (1999) Biochem Pharmacol 57:597–601CrossRefPubMedGoogle Scholar
  27. 27.
    Klinge CM (2001) Nucleic Acids Res 29:2905–2919CrossRefPubMedGoogle Scholar
  28. 28.
    Ogawa S, Eng V, Taylor J, Lubahn DB, Korach KS, Pfaff DW (1998) Endocrinology 139:5070–5081PubMedGoogle Scholar
  29. 29.
    Cowley SM, Hoare S, Mosselman S, Parker MG (1997) J Biol Chem 272:19858–19862PubMedGoogle Scholar
  30. 30.
    Hall JM, McDonnell DP (1999) Endocrinology 140:5566–5578PubMedGoogle Scholar
  31. 31.
    McKenna NJ, O’ Malley BW (2002) Endocrinology 143:2461–2465PubMedGoogle Scholar
  32. 32.
    McKenna NJ, Lanz RB, O’Malley BW (1999) Endocrine Rev 20:321–344Google Scholar
  33. 33.
    Chen JD, Evans RM (1995) Nature 377:454–457CrossRefPubMedGoogle Scholar
  34. 34.
    Horlein AJ, Naar AM, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamei Y, Soderstrom M, Glass CK, Rosenfeld MG (1995) Nature 377:397–404CrossRefPubMedGoogle Scholar
  35. 35.
    Wolffe AP (1997) Cell Res 7:127–142PubMedGoogle Scholar
  36. 36.
    Gardner RM, Kirkland JL, Ireland JS, Stancel GM (1978) Endocrinology 103:1164–1172PubMedGoogle Scholar
  37. 37.
    Vasudevan N, Ogawa S, Pfaff D (2002) Physiol Rev 82:923–944PubMedGoogle Scholar
  38. 38.
    Driggers PH, Segars JH (2002) Trends Endocrinol Metab 13:422–427CrossRefPubMedGoogle Scholar
  39. 39.
    Burow ME, Tang Y, CollinsBurow BM, Krajewski S, Reed JC, McLachlan JA, Beckman BS (1999) Carcinogenesis 20:2057–2061CrossRefPubMedGoogle Scholar
  40. 40.
    Liu G, Schwartz JA, Brooks SC (1999) Biochem Biophys Res Commun 264:359–364PubMedGoogle Scholar
  41. 41.
    Medh RD, Thompson EB (2000) Cell Tissue Res 301:101–124CrossRefPubMedGoogle Scholar
  42. 42.
    Simoncini T, Varone G, Fornari L, Mannella P, Luisi M, Labrie F, Genazzani AR (2002) Endocrinology 143:2052–2061PubMedGoogle Scholar
  43. 43.
    Russell KS, Haynes MP, Sinha D, Clerisme E, Bender JR (2000) Proc Natl Acad Sci USA 97:5930–5935CrossRefPubMedGoogle Scholar
  44. 44.
    Kelly MJ, Qiu J, Wagner EJ, Ronnekleiv OK (2002) J Steroid Biochem Mol Biol 83:187–193CrossRefPubMedGoogle Scholar
  45. 45.
    Kelly MJ, Levin ER (2001) Trends Endocrinol Metab 12:152–156Google Scholar
  46. 46.
    Katzenellenbogen JA, O’Malley BW, Katzenellenbogen BS (1996) Mol Endocrinol 10:119–131PubMedGoogle Scholar
  47. 47.
    O’Connor JC, Davis LG, Frame SR, Cook JC (2000) Toxicol Sci 54:338–354CrossRefPubMedGoogle Scholar
  48. 48.
    Hu X, Lazar MA (2000) Trends Endocrinol Metab 11:6–10CrossRefPubMedGoogle Scholar
  49. 49.
    Shupnik MA (2000) Rev Endocr Metab Disord 1:35–42CrossRefPubMedGoogle Scholar
  50. 50.
    Goldman JM, Laws SC, Balchak SK, Cooper RL, Kavlock RJ (2000) Crit Rev Toxicol 30:135–196PubMedGoogle Scholar
  51. 51.
    Vinggaard AM, Nellemann C, Dalgaard M, Jorgensen EB, Andersen HR (2002) Toxicol Sci 69:344–353CrossRefPubMedGoogle Scholar
  52. 52.
    Hartig PC, Bobseine KL, Britt BH, Cardon MC, Lambright CR, Wilson VS, Gray LE Jr (2002) Toxicol Sci 66:82–90CrossRefPubMedGoogle Scholar
  53. 53.
    OECD (2001) Appraisal of test methods for sex hormone disrupting chemicals. In: OECD Environment Health and Safety Publications Series on Testing and Assessment No 21. Environment Directorate OECD, ParisGoogle Scholar
  54. 54.
    Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson J (1997) Endocrinology 138:863–870PubMedGoogle Scholar
  55. 55.
    Bolger R, Wiese TE, Ervin K, Nestich S, Checovich W (1998) Environ Health Perspect 106:551–557PubMedGoogle Scholar
  56. 56.
    Mueller SO, Kling M, Arifin Firzani P, Mecky A, Duranti E, Shields-Botella J, Delansorne R, Broschard T, Kramer P-J (2003) Toxicol Lett 142:89–101CrossRefPubMedGoogle Scholar
  57. 57.
    Shelby MD, Newbold RR, Tully D, Chae K, Davis VL (1996) Environ Health Perspect 104:1296–1300PubMedGoogle Scholar
  58. 58.
    Makela S, Davis VL, Tally WC, Korkman J, Salo L, Vihko R, Santti R, Korach KS (1994) Environ Health Perspect 102:572–578PubMedGoogle Scholar
  59. 59.
    McDonnell DP (1999) Trends Endocrinol Metab 10:301–311CrossRefPubMedGoogle Scholar
  60. 60.
    Ramamoorthy K, Vyhlidal C, Wang F, Chen IC, Safe S, McDonnell DP, Leonard LS, Gaido KW (1997) Tox Appl Pharmacol 147(1):93–100CrossRefGoogle Scholar
  61. 61.
    Breithofer A, Graumann K, Scicchitano MS, Karathanasis SK, Butt TR, Jungbauer A (1998) J Steroid Biochem Mol Biol 67:421–429CrossRefPubMedGoogle Scholar
  62. 62.
    Jiang SY, Jordan VC (1992) J Natl Cancer Inst 84:580–591PubMedGoogle Scholar
  63. 63.
    Mueller SO, Hall JM, Swope DL, Pedersen LC, Korach KS (2003) J Biol Chem 278:12255–12262CrossRefPubMedGoogle Scholar
  64. 64.
    Legler J, van den Brink CE, Brouwer A, Murk AJ, van der Saag PT, Vethaak AD, van der Burg B (1999) Toxicol Sci 48:55–66CrossRefPubMedGoogle Scholar
  65. 65.
    Rogers JM, Denison MS (2000) In Vitro Mol Toxicol 13:67–82Google Scholar
  66. 66.
    Mueller SO, Korach KS (2001) J Androl 22:652–664PubMedGoogle Scholar
  67. 67.
    Mak P, Cruz FD, Chen S (1999) Environ Health Perspect 107:855–860PubMedGoogle Scholar
  68. 68.
    Pelissero C, Lenczowski MJ, Chinzi D, Davail-Cuisset B, Sumpter JP, Fostier A (1996) J Steroid Biochem Mol Biol 57:215–223CrossRefPubMedGoogle Scholar
  69. 69.
    Gray LE (1998) Toxicol Lett 103:677–680CrossRefGoogle Scholar
  70. 70.
    Laskey JW, Berman E, Ferrell JM (1995) Reprod Toxicol 9:131–141PubMedGoogle Scholar
  71. 71.
    Zhou G, Cummings R, Li Y, Mitra S, Wilkinson HA, Elbrecht A, Hermes JD, Schaeffer JM, Smith RG, Moller DE (1998) Mol Endocrinol 12:1594–1604PubMedGoogle Scholar
  72. 72.
    Routledge EJ, White R, Parker MG, Sumpter JP (2000) J Biol Chem 275:35986–35993CrossRefPubMedGoogle Scholar
  73. 73.
    Jorgensen M, Vendelbo B, Skakkebaek NE, Leffers H (2000) Environ Health Perspect 108:403–412PubMedGoogle Scholar
  74. 74.
    An JP, Tzagarakis-Foster C, Scharschmidt TC, Lomri N, Leitman DC (2001) J Biol Chem 276:17808–17814CrossRefPubMedGoogle Scholar
  75. 75.
    Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO (1995) Environ Health Perspect 103:113–122Google Scholar
  76. 76.
    Nikov GN, Hopkins NE, Boue S, Alworth WL (2000) Environ Health Perspect 108:867–872PubMedGoogle Scholar
  77. 77.
    Boyer M, Poujol N, Margeat E, Royer CA (2000) Nucleic Acids Res 28:2494–2502CrossRefPubMedGoogle Scholar
  78. 78.
    Nuwaysir EF, Bittner M, Trent J, Barrett JC, Afshari CA (1999) Mol Carcinog 24:153–159Google Scholar
  79. 79.
    Holinka CF, Hata H, Kuramoto H, Gurpide E (1986) Cancer Res 46:2771–2774PubMedGoogle Scholar
  80. 80.
    Sanderson JT, Boerma J, Lansbergen GWA, van den Berg M (2002) Tox Appl Pharmacol 182:44–54CrossRefGoogle Scholar
  81. 81.
    Ando S, Sirianni R, Forastieri P, Casaburi I, Lanzino M, Rago V, Giordano F, Giordano C, Carpino A, Pezzi V (2001) Mol Cell Endocrinol 178:11–21CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Molecular Toxicology, Institute of ToxicologyMerck KGaADarmstadtGermany

Personalised recommendations