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. 1998 Apr;106(Suppl 2):577–582. doi: 10.1289/ehp.98106577

Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays.

T Zacharewski 1
PMCID: PMC1533380  PMID: 9599705

Abstract

It has been suggested that chemicals and complex mixtures capable of modulating the endocrine system may contribute to adverse health, reproduction, and developmental effects in humans and wildlife. These effects include increased incidence of hormone-dependent cancers, compromised reproductive fitness, and abnormal reproductive system development. In response to public concern, regulatory agencies in North America and Europe are formulating potential strategies to systematically test chemicals and complex mixtures for their endocrine-disrupting activities. Because of the complexity of the endocrine system and the number of potential endocrine disruptor targets, a tiered approach involving a complementary battery of short- and long-term in vivo and in vitro assays that assesses both receptor and nonreceptor-mediated mechanisms of action is being considered. However, the available established assays use a limited number of end points, and significant information gaps exist for other potential targets in the endocrine system. In addition to discussing the merits and limitations of the assays that may be adopted, this paper also highlights potential problems associated with the use of a tiered testing strategy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adami H. O., Bergström R., Möhner M., Zatoński W., Storm H., Ekbom A., Tretli S., Teppo L., Ziegler H., Rahu M. Testicular cancer in nine northern European countries. Int J Cancer. 1994 Oct 1;59(1):33–38. doi: 10.1002/ijc.2910590108. [DOI] [PubMed] [Google Scholar]
  2. Adlercreutz H., Fotsis T., Heikkinen R., Dwyer J. T., Woods M., Goldin B. R., Gorbach S. L. Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet. 1982 Dec 11;2(8311):1295–1299. doi: 10.1016/s0140-6736(82)91507-0. [DOI] [PubMed] [Google Scholar]
  3. Ahlborg U. G., Lipworth L., Titus-Ernstoff L., Hsieh C. C., Hanberg A., Baron J., Trichopoulos D., Adami H. O. Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidence. Crit Rev Toxicol. 1995;25(6):463–531. doi: 10.3109/10408449509017924. [DOI] [PubMed] [Google Scholar]
  4. Arai Y., Mori T., Suzuki Y., Bern H. A. Long-term effects of perinatal exposure to sex steroids and diethylstilbestrol on the reproductive system of male mammals. Int Rev Cytol. 1983;84:235–268. doi: 10.1016/s0074-7696(08)61019-0. [DOI] [PubMed] [Google Scholar]
  5. Arnold S. F., Robinson M. K., Notides A. C., Guillette L. J., Jr, McLachlan J. A. A yeast estrogen screen for examining the relative exposure of cells to natural and xenoestrogens. Environ Health Perspect. 1996 May;104(5):544–548. doi: 10.1289/ehp.96104544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Balaguer P., Joyeux A., Denison M. S., Vincent R., Gillesby B. E., Zacharewski T. Assessing the estrogenic and dioxin-like activities of chemicals and complex mixtures using in vitro recombinant receptor-reporter gene assays. Can J Physiol Pharmacol. 1996 Feb;74(2):216–222. [PubMed] [Google Scholar]
  7. Barnes S., Grubbs C., Setchell K. D., Carlson J. Soybeans inhibit mammary tumors in models of breast cancer. Prog Clin Biol Res. 1990;347:239–253. [PubMed] [Google Scholar]
  8. Carlsen E., Giwercman A., Keiding N., Skakkebaek N. E. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12;305(6854):609–613. doi: 10.1136/bmj.305.6854.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carter H. B., Coffey D. S. The prostate: an increasing medical problem. Prostate. 1990;16(1):39–48. doi: 10.1002/pros.2990160105. [DOI] [PubMed] [Google Scholar]
  10. Chiarodo A. National Cancer Institute roundtable on prostate cancer: future research directions. Cancer Res. 1991 May 1;51(9):2498–2505. [PubMed] [Google Scholar]
  11. Colborn T., vom Saal F. S., Soto A. M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993 Oct;101(5):378–384. doi: 10.1289/ehp.93101378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Connor K., Howell J., Chen I., Liu H., Berhane K., Sciarretta C., Safe S., Zacharewski T. Failure of chloro-S-triazine-derived compounds to induce estrogen receptor-mediated responses in vivo and in vitro. Fundam Appl Toxicol. 1996 Mar;30(1):93–101. [PubMed] [Google Scholar]
  13. DORFMAN R. I., DORFMAN A. S. Estrogen assays using the rat uterus. Endocrinology. 1954 Jul;55(1):65–69. doi: 10.1210/endo-55-1-65. [DOI] [PubMed] [Google Scholar]
  14. DRILL V. A. ENDOCRINE PROPERTIES AND LONG-TERM SAFETY OF ORAL CONTRACEPTIVES. Metabolism. 1965 Mar;14:SUPPL–SUPPL:310. doi: 10.1016/0026-0495(65)90016-8. [DOI] [PubMed] [Google Scholar]
  15. Damassa D. A., Lin T. M., Sonnenschein C., Soto A. M. Biological effects of sex hormone-binding globulin on androgen-induced proliferation and androgen metabolism in LNCaP prostate cells. Endocrinology. 1991 Jul;129(1):75–84. doi: 10.1210/endo-129-1-75. [DOI] [PubMed] [Google Scholar]
  16. Davis D. L., Bradlow H. L., Wolff M., Woodruff T., Hoel D. G., Anton-Culver H. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect. 1993 Oct;101(5):372–377. doi: 10.1289/ehp.93101372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Depue R. H. Maternal and gestational factors affecting the risk of cryptorchidism and inguinal hernia. Int J Epidemiol. 1984 Sep;13(3):311–318. doi: 10.1093/ije/13.3.311. [DOI] [PubMed] [Google Scholar]
  18. Eil C., Nisula B. C. The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin. J Steroid Biochem. 1990 Mar;35(3-4):409–414. doi: 10.1016/0022-4731(90)90248-q. [DOI] [PubMed] [Google Scholar]
  19. Falck F., Jr, Ricci A., Jr, Wolff M. S., Godbold J., Deckers P. Pesticides and polychlorinated biphenyl residues in human breast lipids and their relation to breast cancer. Arch Environ Health. 1992 Mar-Apr;47(2):143–146. [PubMed] [Google Scholar]
  20. Fisch H., Goluboff E. T. Geographic variations in sperm counts: a potential cause of bias in studies of semen quality. Fertil Steril. 1996 May;65(5):1044–1046. doi: 10.1016/s0015-0282(16)58284-3. [DOI] [PubMed] [Google Scholar]
  21. Fisch H., Goluboff E. T., Olson J. H., Feldshuh J., Broder S. J., Barad D. H. Semen analyses in 1,283 men from the United States over a 25-year period: no decline in quality. Fertil Steril. 1996 May;65(5):1009–1014. doi: 10.1016/s0015-0282(16)58278-8. [DOI] [PubMed] [Google Scholar]
  22. Forman D., Møller H. Testicular cancer. Cancer Surv. 1994;19-20:323–341. [PubMed] [Google Scholar]
  23. Fortunati N., Fissore F., Fazzari A., Berta L., Benedusi-Pagliano E., Frairia R. Biological relevance of the interaction between sex steroid binding protein and its specific receptor of MCF-7 cells: effect on the estradiol-induced cell proliferation. J Steroid Biochem Mol Biol. 1993 May;45(5):435–444. doi: 10.1016/0960-0760(93)90012-l. [DOI] [PubMed] [Google Scholar]
  24. Fortunati N., Fissore F., Fazzari A., Berta L., Giudici M., Frairia R. Sex steroid-binding protein interacts with a specific receptor on human premenopausal endometrium membrane: modulating effect of estradiol. Steroids. 1991 Jun;56(6):341–346. doi: 10.1016/0039-128x(91)90058-4. [DOI] [PubMed] [Google Scholar]
  25. Fortunati N., Fissore F., Fazzari A., Berta L., Varvello L., Frairia R. Receptor for sex steroid-binding protein of endometrium membranes: solubilization, partial characterization, and role of estradiol in steroid-binding protein-soluble receptor interaction. Steroids. 1992 Sep;57(9):464–470. doi: 10.1016/0039-128x(92)90102-f. [DOI] [PubMed] [Google Scholar]
  26. Fortunati N., Frairia R., Fissore F., Berta L., Fazzari A., Gaidano G. The receptor for human sex steroid binding protein (SBP) is expressed on membranes of neoplastic endometrium. J Steroid Biochem Mol Biol. 1992 Apr;42(2):185–191. doi: 10.1016/0960-0760(92)90027-g. [DOI] [PubMed] [Google Scholar]
  27. Gellert R. J. Kepone, mirex, dieldrin, and aldrin: estrogenic activity and the induction of persistent vaginal estrus and anovulation in rats following neonatal treatment. Environ Res. 1978 Jul;16(1-3):131–138. doi: 10.1016/0013-9351(78)90150-0. [DOI] [PubMed] [Google Scholar]
  28. Gierthy J. F., Lincoln D. W., 2nd, Roth K. E., Bowser S. S., Bennett J. A., Bradley L., Dickerman H. W. Estrogen-stimulation of postconfluent cell accumulation and foci formation of human MCF-7 breast cancer cells. J Cell Biochem. 1991 Feb;45(2):177–187. doi: 10.1002/jcb.240450209. [DOI] [PubMed] [Google Scholar]
  29. Giwercman A., Skakkebaek N. E. The human testis--an organ at risk? Int J Androl. 1992 Oct;15(5):373–375. doi: 10.1111/j.1365-2605.1992.tb01351.x. [DOI] [PubMed] [Google Scholar]
  30. Glass A. G., Hoover R. N. Rising incidence of breast cancer: relationship to stage and receptor status. J Natl Cancer Inst. 1990 Apr 18;82(8):693–696. doi: 10.1093/jnci/82.8.693. [DOI] [PubMed] [Google Scholar]
  31. HISAW F. L., Jr Comparative effectiveness of estrogens on fluid imbibition and growth of the rat's uterus. Endocrinology. 1959 Feb;64(2):276–289. doi: 10.1210/endo-64-2-276. [DOI] [PubMed] [Google Scholar]
  32. Hammond G. L., Lähteenmäki P. L. A versatile method for the determination of serum cortisol binding globulin and sex hormone binding globulin binding capacities. Clin Chim Acta. 1983 Jul 31;132(1):101–110. doi: 10.1016/0009-8981(83)90237-1. [DOI] [PubMed] [Google Scholar]
  33. Hammond G. L. Molecular properties of corticosteroid binding globulin and the sex-steroid binding proteins. Endocr Rev. 1990 Feb;11(1):65–79. doi: 10.1210/edrv-11-1-65. [DOI] [PubMed] [Google Scholar]
  34. Henderson B. E., Ross R., Bernstein L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res. 1988 Jan 15;48(2):246–253. [PubMed] [Google Scholar]
  35. Herbst A. L., Ulfelder H., Poskanzer D. C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878–881. doi: 10.1056/NEJM197104222841604. [DOI] [PubMed] [Google Scholar]
  36. Hirano T., Fukuoka K., Oka K., Naito T., Hosaka K., Mitsuhashi H., Matsumoto Y. Antiproliferative activity of mammalian lignan derivatives against the human breast carcinoma cell line, ZR-75-1. Cancer Invest. 1990;8(6):595–602. doi: 10.3109/07357909009018926. [DOI] [PubMed] [Google Scholar]
  37. Hryb D. J., Khan M. S., Romas N. A., Rosner W. Solubilization and partial characterization of the sex hormone-binding globulin receptor from human prostate. J Biol Chem. 1989 Apr 5;264(10):5378–5383. [PubMed] [Google Scholar]
  38. Hryb D. J., Khan M. S., Romas N. A., Rosner W. The control of the interaction of sex hormone-binding globulin with its receptor by steroid hormones. J Biol Chem. 1990 Apr 15;265(11):6048–6054. [PubMed] [Google Scholar]
  39. Hryb D. J., Khan M. S., Rosner W. Testosterone-estradiol-binding globulin binds to human prostatic cell membranes. Biochem Biophys Res Commun. 1985 Apr 16;128(1):432–440. doi: 10.1016/0006-291x(85)91697-3. [DOI] [PubMed] [Google Scholar]
  40. Ignar-Trowbridge D. M., Nelson K. G., Bidwell M. C., Curtis S. W., Washburn T. F., McLachlan J. A., Korach K. S. Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4658–4662. doi: 10.1073/pnas.89.10.4658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ingraham H. A., Lala D. S., Ikeda Y., Luo X., Shen W. H., Nachtigal M. W., Abbud R., Nilson J. H., Parker K. L. The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis. Genes Dev. 1994 Oct 1;8(19):2302–2312. doi: 10.1101/gad.8.19.2302. [DOI] [PubMed] [Google Scholar]
  42. Jackson M. B. The epidemiology of cryptorchidism. John Radcliffe Hospital Cryptorchidism Research Group. Horm Res. 1988;30(4-5):153–156. doi: 10.1159/000181052. [DOI] [PubMed] [Google Scholar]
  43. Janowski B. A., Willy P. J., Devi T. R., Falck J. R., Mangelsdorf D. J. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996 Oct 24;383(6602):728–731. doi: 10.1038/383728a0. [DOI] [PubMed] [Google Scholar]
  44. Jansen H. T., Cooke P. S., Porcelli J., Liu T. C., Hansen L. G. Estrogenic and antiestrogenic actions of PCBs in the female rat: in vitro and in vivo studies. Reprod Toxicol. 1993 May-Jun;7(3):237–248. doi: 10.1016/0890-6238(93)90230-5. [DOI] [PubMed] [Google Scholar]
  45. Jobling S., Reynolds T., White R., Parker M. G., Sumpter J. P. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect. 1995 Jun;103(6):582–587. doi: 10.1289/ehp.95103582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Jones R. C., Edgren R. A. The effects of various steroids on the vaginal histology in the rat. Fertil Steril. 1973 Apr;24(4):284–291. doi: 10.1016/s0015-0282(16)39613-3. [DOI] [PubMed] [Google Scholar]
  47. Kelce W. R., Stone C. R., Laws S. C., Gray L. E., Kemppainen J. A., Wilson E. M. Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature. 1995 Jun 15;375(6532):581–585. doi: 10.1038/375581a0. [DOI] [PubMed] [Google Scholar]
  48. Khalil M. W., Morley P., Glasier M. A., Armstrong D. T., Lang T. Formation of 4-oestrene-3,17-dione (19-norandrostenedione) by porcine granulosa cells in vitro is inhibited by the aromatase inhibitor 4-hydroxyandrostenedione and the cytochrome P-450 inhibitors aminoglutethimide phosphate and ketoconazole. J Endocrinol. 1989 Feb;120(2):251–260. doi: 10.1677/joe.0.1200251. [DOI] [PubMed] [Google Scholar]
  49. Korach K. S., McLachlan J. A. Techniques for detection of estrogenicity. Environ Health Perspect. 1995 Oct;103 (Suppl 7):5–8. doi: 10.1289/ehp.95103s75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Korach K. S. Surprising places of estrogenic activity. Endocrinology. 1993 Jun;132(6):2277–2278. doi: 10.1210/endo.132.6.8504730. [DOI] [PubMed] [Google Scholar]
  51. Krishnan A. V., Stathis P., Permuth S. F., Tokes L., Feldman D. Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology. 1993 Jun;132(6):2279–2286. doi: 10.1210/endo.132.6.8504731. [DOI] [PubMed] [Google Scholar]
  52. Kuiper G. G., Enmark E., Pelto-Huikko M., Nilsson S., Gustafsson J. A. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925–5930. doi: 10.1073/pnas.93.12.5925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Lans M. C., Klasson-Wehler E., Willemsen M., Meussen E., Safe S., Brouwer A. Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, -dibenzo-p-dioxins and -dibenzofurans with human transthyretin. Chem Biol Interact. 1993 Jul;88(1):7–21. doi: 10.1016/0009-2797(93)90081-9. [DOI] [PubMed] [Google Scholar]
  54. Laskey J. W., Berman E. Steroidogenic assessment using ovary culture in cycling rats: effects of bis(2-diethylhexyl)phthalate on ovarian steroid production. Reprod Toxicol. 1993;7(1):25–33. doi: 10.1016/0890-6238(93)90006-s. [DOI] [PubMed] [Google Scholar]
  55. Laskey J. W., Klinefelter G. R., Kelce W. R., Ewing L. L. Effects of ethane dimethanesulfonate (EDS) on adult and immature rabbit Leydig cells: comparison with EDS-treated rat Leydig cells. Biol Reprod. 1994 May;50(5):1151–1160. doi: 10.1095/biolreprod50.5.1151. [DOI] [PubMed] [Google Scholar]
  56. Luo X., Ikeda Y., Schlosser D. A., Parker K. L. Steroidogenic factor 1 is the essential transcript of the mouse Ftz-F1 gene. Mol Endocrinol. 1995 Sep;9(9):1233–1239. doi: 10.1210/mend.9.9.7491115. [DOI] [PubMed] [Google Scholar]
  57. MARTIN L., CLARINGBOLD P. J. The mitogenic action of oestrogens in the vaginal epithelium of the ovariectomized mouse. J Endocrinol. 1960 May;20:173–186. doi: 10.1677/joe.0.0200173. [DOI] [PubMed] [Google Scholar]
  58. Mangelsdorf D. J., Thummel C., Beato M., Herrlich P., Schütz G., Umesono K., Blumberg B., Kastner P., Mark M., Chambon P. The nuclear receptor superfamily: the second decade. Cell. 1995 Dec 15;83(6):835–839. doi: 10.1016/0092-8674(95)90199-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Mani S. K., Allen J. M., Clark J. H., Blaustein J. D., O'Malley B. W. Convergent pathways for steroid hormone- and neurotransmitter-induced rat sexual behavior. Science. 1994 Aug 26;265(5176):1246–1249. doi: 10.1126/science.7915049. [DOI] [PubMed] [Google Scholar]
  60. Martin P. M., Horwitz K. B., Ryan D. S., McGuire W. L. Phytoestrogen interaction with estrogen receptors in human breast cancer cells. Endocrinology. 1978 Nov;103(5):1860–1867. doi: 10.1210/endo-103-5-1860. [DOI] [PubMed] [Google Scholar]
  61. McLachlan J. A., Korach K. S., Newbold R. R., Degen G. H. Diethylstilbestrol and other estrogens in the environment. Fundam Appl Toxicol. 1984 Oct;4(5):686–691. doi: 10.1016/0272-0590(84)90089-7. [DOI] [PubMed] [Google Scholar]
  62. McLachlan J. A., Newbold R. R., Bullock B. Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol. Science. 1975 Dec 5;190(4218):991–992. doi: 10.1126/science.242076. [DOI] [PubMed] [Google Scholar]
  63. McLachlan J. A. Prenatal exposure to diethylstilbestrol in mice: toxicological studies. J Toxicol Environ Health. 1977 Jan;2(3):527–537. doi: 10.1080/15287397709529453. [DOI] [PubMed] [Google Scholar]
  64. Messina M. J., Persky V., Setchell K. D., Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21(2):113–131. doi: 10.1080/01635589409514310. [DOI] [PubMed] [Google Scholar]
  65. Miksicek R. J. Commonly occurring plant flavonoids have estrogenic activity. Mol Pharmacol. 1993 Jul;44(1):37–43. [PubMed] [Google Scholar]
  66. Miller W. R. Endocrine treatment for breast cancers: biological rationale and current progress. J Steroid Biochem Mol Biol. 1990 Nov 30;37(4):467–480. doi: 10.1016/0960-0760(90)90390-7. [DOI] [PubMed] [Google Scholar]
  67. Moore M., Mustain M., Daniel K., Chen I., Safe S., Zacharewski T., Gillesby B., Joyeux A., Balaguer P. Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum. Toxicol Appl Pharmacol. 1997 Jan;142(1):160–168. doi: 10.1006/taap.1996.8022. [DOI] [PubMed] [Google Scholar]
  68. Nakhla A. M., Khan M. S., Romas N. P., Rosner W. Estradiol causes the rapid accumulation of cAMP in human prostate. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5402–5405. doi: 10.1073/pnas.91.12.5402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Nakhla A. M., Khan M. S., Rosner W. Biologically active steroids activate receptor-bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3',5'-monophosphate. J Clin Endocrinol Metab. 1990 Aug;71(2):398–404. doi: 10.1210/jcem-71-2-398. [DOI] [PubMed] [Google Scholar]
  70. Nakhla A. M., Rosner W. Stimulation of prostate cancer growth by androgens and estrogens through the intermediacy of sex hormone-binding globulin. Endocrinology. 1996 Oct;137(10):4126–4129. doi: 10.1210/endo.137.10.8828467. [DOI] [PubMed] [Google Scholar]
  71. Nazareth L. V., Weigel N. L. Activation of the human androgen receptor through a protein kinase A signaling pathway. J Biol Chem. 1996 Aug 16;271(33):19900–19907. doi: 10.1074/jbc.271.33.19900. [DOI] [PubMed] [Google Scholar]
  72. Nelson J. A., Struck R. F., James R. Estrogenic activities of chlorinated hydrocarbons. J Toxicol Environ Health. 1978 Mar-May;4(2-3):325–339. doi: 10.1080/15287397809529664. [DOI] [PubMed] [Google Scholar]
  73. Newman P. A. Breast cancer incidence is on the rise--but why? J Natl Cancer Inst. 1990 Jun 20;82(12):998–1000. doi: 10.1093/jnci/82.12.998. [DOI] [PubMed] [Google Scholar]
  74. Nimrod A. C., Benson W. H. Environmental estrogenic effects of alkylphenol ethoxylates. Crit Rev Toxicol. 1996 May;26(3):335–364. doi: 10.3109/10408449609012527. [DOI] [PubMed] [Google Scholar]
  75. Osterlind A. Diverging trends in incidence and mortality of testicular cancer in Denmark, 1943-1982. Br J Cancer. 1986 Apr;53(4):501–505. doi: 10.1038/bjc.1986.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Pappas T. C., Gametchu B., Watson C. S. Membrane estrogen receptors identified by multiple antibody labeling and impeded-ligand binding. FASEB J. 1995 Mar;9(5):404–410. doi: 10.1096/fasebj.9.5.7896011. [DOI] [PubMed] [Google Scholar]
  77. Paulsen C. A., Berman N. G., Wang C. Data from men in greater Seattle area reveals no downward trend in semen quality: further evidence that deterioration of semen quality is not geographically uniform. Fertil Steril. 1996 May;65(5):1015–1020. [PubMed] [Google Scholar]
  78. Porto C. S., Gunsalus G. L., Bardin C. W., Phillips D. M., Musto N. A. Receptor-mediated endocytosis of an extracellular steroid-binding protein (TeBG) in MCF-7 human breast cancer cells. Endocrinology. 1991 Jul;129(1):436–445. doi: 10.1210/endo-129-1-436. [DOI] [PubMed] [Google Scholar]
  79. Prener A., Hsieh C. C., Engholm G., Trichopoulos D., Jensen O. M. Birth order and risk of testicular cancer. Cancer Causes Control. 1992 May;3(3):265–272. doi: 10.1007/BF00124260. [DOI] [PubMed] [Google Scholar]
  80. RUBIN B. L., DORFMAN A. S., BLACK L., DORFMAN R. I. Bioassay of estrogens using the mouse uterine response. Endocrinology. 1951 Oct;49(4):429–439. doi: 10.1210/endo-49-4-429. [DOI] [PubMed] [Google Scholar]
  81. Reel J. R., Lamb IV J. C., Neal B. H. Survey and assessment of mammalian estrogen biological assays for hazard characterization. Fundam Appl Toxicol. 1996 Dec;34(2):288–305. doi: 10.1006/faat.1996.0198. [DOI] [PubMed] [Google Scholar]
  82. Rosner W. The functions of corticosteroid-binding globulin and sex hormone-binding globulin: recent advances. Endocr Rev. 1990 Feb;11(1):80–91. doi: 10.1210/edrv-11-1-80. [DOI] [PubMed] [Google Scholar]
  83. Safe S. H. Environmental and dietary estrogens and human health: is there a problem? Environ Health Perspect. 1995 Apr;103(4):346–351. doi: 10.1289/ehp.95103346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Safe S. H. Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Pharmacol Ther. 1995;67(2):247–281. doi: 10.1016/0163-7258(95)00017-b. [DOI] [PubMed] [Google Scholar]
  85. Santen R. J., Manni A., Harvey H., Redmond C. Endocrine treatment of breast cancer in women. Endocr Rev. 1990 May;11(2):221–265. doi: 10.1210/edrv-11-2-221. [DOI] [PubMed] [Google Scholar]
  86. Shalev A., Siegrist-Kaiser C. A., Yen P. M., Wahli W., Burger A. G., Chin W. W., Meier C. A. The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin. Endocrinology. 1996 Oct;137(10):4499–4502. doi: 10.1210/endo.137.10.8828512. [DOI] [PubMed] [Google Scholar]
  87. Sharpe R. M. Reproductive biology. Another DDT connection. Nature. 1995 Jun 15;375(6532):538–539. doi: 10.1038/375538a0. [DOI] [PubMed] [Google Scholar]
  88. Sharpe R. M., Skakkebaek N. E. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993 May 29;341(8857):1392–1395. doi: 10.1016/0140-6736(93)90953-e. [DOI] [PubMed] [Google Scholar]
  89. Soto A. M., Sonnenschein C., Chung K. L., Fernandez M. F., Olea N., Serrano F. O. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995 Oct;103 (Suppl 7):113–122. doi: 10.1289/ehp.95103s7113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Spitz M. R., Sider J. G., Pollack E. S., Lynch H. K., Newell G. R. Incidence and descriptive features of testicular cancer among United States whites, blacks, and Hispanics, 1973-1982. Cancer. 1986 Oct 15;58(8):1785–1790. doi: 10.1002/1097-0142(19861015)58:8<1785::aid-cncr2820580836>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  91. Strel'chyonok O. A., Avvakumov G. V. Specific steroid-binding glycoproteins of human blood plasma: novel data on their structure and function. J Steroid Biochem. 1990 Apr;35(5):519–534. doi: 10.1016/0022-4731(90)90195-x. [DOI] [PubMed] [Google Scholar]
  92. Strel'chyonok O. A., Avvakumov G. V., Survilo L. I. A recognition system for sex-hormone-binding protein-estradiol complex in human decidual endometrium plasma membranes. Biochim Biophys Acta. 1984 Dec 20;802(3):459–466. doi: 10.1016/0304-4165(84)90365-9. [DOI] [PubMed] [Google Scholar]
  93. Terenius L. The Allen-Doisy test for estrogens reinvestigated. Steroids. 1971 Jun;17(6):653–661. doi: 10.1016/0039-128x(71)90081-x. [DOI] [PubMed] [Google Scholar]
  94. Watson C. S., Pappas T. C., Gametchu B. The other estrogen receptor in the plasma membrane: implications for the actions of environmental estrogens. Environ Health Perspect. 1995 Oct;103 (Suppl 7):41–50. doi: 10.1289/ehp.95103s741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. White R., Jobling S., Hoare S. A., Sumpter J. P., Parker M. G. Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology. 1994 Jul;135(1):175–182. doi: 10.1210/endo.135.1.8013351. [DOI] [PubMed] [Google Scholar]
  96. Wiese T. E., Kral L. G., Dennis K. E., Butler W. B., Brooks S. C. Optimization of estrogen growth response in MCF-7 cells. In Vitro Cell Dev Biol. 1992 Sep-Oct;28A(9-10):595–602. doi: 10.1007/BF02631033. [DOI] [PubMed] [Google Scholar]
  97. Wilcox A. J., Baird D. D., Weinberg C. R., Hornsby P. P., Herbst A. L. Fertility in men exposed prenatally to diethylstilbestrol. N Engl J Med. 1995 May 25;332(21):1411–1416. doi: 10.1056/NEJM199505253322104. [DOI] [PubMed] [Google Scholar]
  98. Wilkinson T. J., Colls B. M., Schluter P. J. Increased incidence of germ cell testicular cancer in New Zealand Maoris. Br J Cancer. 1992 May;65(5):769–771. doi: 10.1038/bjc.1992.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Willett W. The search for the causes of breast and colon cancer. Nature. 1989 Mar 30;338(6214):389–394. doi: 10.1038/338389a0. [DOI] [PubMed] [Google Scholar]
  100. Wilson E. M., French F. S. Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. J Biol Chem. 1976 Sep 25;251(18):5620–5629. [PubMed] [Google Scholar]
  101. Wolff M. S., Toniolo P. G., Lee E. W., Rivera M., Dubin N. Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst. 1993 Apr 21;85(8):648–652. doi: 10.1093/jnci/85.8.648. [DOI] [PubMed] [Google Scholar]

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