Unexpected Estrogenicity of Endocrine Disruptors may Evoke a Failure of Pregnancy Derived from Uterine Function: Overview of Their Possible Mechanism(s) through Steroid Receptors

  • Dang, V.H. (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University) ;
  • Nguyen, T.H. (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University) ;
  • Choi, K.C. (Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia) ;
  • Jeung, E.B. (Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University)
  • Published : 2007.12.31

Abstract

Although many studies have focused on the biological and toxicological effects of phenol products, in particular, in reproductive tracts, the data about their effects in this estrogenic responsive tissue are much less clear. In addition, the in vitro and in vivo data concerning ED-adverse impacts in other endocrine organs, i.e. pituitary gland, are not understood well either. Thus, a further study is needed for providing a new insight into possible impacts of estrogenic EDs including phenol products in humans and wildlife. A combination of in vitro and in vivo system for examining EDs may bring better understanding into the regulatory mechanisms underlying EDs-induced events. In addition, this information may support for developing optimal screening methods of estrogenic EDs, in particular, phenol products.

Keywords

References

  1. An BS, Choi KC, Kang SK, Hwang WS and Jeung EB. 2003. Novel Ca1bindin-D(9k) protein as a useful biomarker for environmental estrogenic compounds in the uterus of immature rats. Reprod. Toxicol., 17:311-319 https://doi.org/10.1016/S0890-6238(03)00003-0
  2. An BS, Kang SK, Shin JH and Jeung EB. 2002. Stimulation of calbindin-D(9k) mRNA expression in the rat uterus by octyl-phenol, nonylphenol and bisphenol. Mol. Cell. Endocrinol., 191:177-186 https://doi.org/10.1016/S0303-7207(02)00042-4
  3. Angel P and Karin M. 1991. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta., 1072:129-157
  4. Armbrecht HJ, Boltz M, Strong R, Richardson A, Bruns ME and Christakos S. 1989. Expression of calbindin-D decreases with age in intestine and kidney. Endocrinology, 125: 2950-2956 https://doi.org/10.1210/endo-125-6-2950
  5. Arnold SF, Robinson MK, Notides AC, Guillette LJ and McLachlan JA. 1996. A yeast estrogen screen for examining the relative exposure of cells to natural and xenoestrogens. Environ. Health. Perspect., 104:544-548 https://doi.org/10.2307/3432996
  6. Baker ME. 1997. Steroid receptor phylogeny and vertebrate origins. Mol. Cell. Endocrinol., 135:101-107 https://doi.org/10.1016/S0303-7207(97)00207-4
  7. Balaguer P, Francois F, Comunale F, Fenet H, Boussioux AM, Pons M, Nicolas JC and Casellas C. 1999. Reporter cell lines to study the estrogenic effects of xenoestrogens. Sci. Total. Environ., 233:47-56 https://doi.org/10.1016/S0048-9697(99)00178-3
  8. Bardin A, Boulle N, Lazennec G, Vignon F and Pujol P. 2004. Loss of ERbeta expression as a common step in estrogendependent tumor progression. Endocr. Relat. Cancer., 11: 537-551 https://doi.org/10.1677/erc.1.00800
  9. Bigsby RM and Young PC. 1994. Estrogenic effects of the antiprogestin onapristone (ZK98.299) in the rodent uterus. Am. J. Obstet. Gynecol., 171:188-194 https://doi.org/10.1016/0002-9378(94)90468-5
  10. Bolger R, Wiese TE, Ervin K, Nestich Sand Checovich W. 1998. Rapid screening of environmental chemicals for estrogen receptor binding capacity. Environ. Health. Perspect., 106:551-557 https://doi.org/10.2307/3434229
  11. Brown EO, Sundstrom SA, Komm BS, Yi Z, Teuscher C and Lyttle CR. 1990. Progesterone regu1ation of estradiol-induced rat uterine secretory protein, complement C3. Biol. Reprod., 42:713-719 https://doi.org/10.1095/biolreprod42.4.713
  12. Bulayeva NN, Gametchu B and Watson CS. 2004. Quantitative measurement of estrogen-induced ERK I and 2 activation via multiple membrane-initiated signaling pathways. Steroids., 69:181-192 https://doi.org/10.1016/j.steroids.2003.12.003
  13. Bulger WH, Muccitelli RM and Kupfer D. 1978. Interactions of methoxychlor, methoxychlor base-soluble contaminant, and 2,2-bis(p-hydroxyphenyl)-1, 1, 1-trichloroethane with rat uterine estrogen receptor. J. Toxicol. Environ. Health, 4: 881-893 https://doi.org/10.1080/15287397809529709
  14. Byrne JA, Mattei MG and Basset P. 1996. Definition of the tumor protein D52 (TPD52) gene family through cloning of D52 homologues in human (hD53) and mouse (mD52). Genomics., 35:523-532 https://doi.org/10.1006/geno.1996.0393
  15. Certa H, Fedtke N, Wiegand HJ, Muller AM and Bolt HM. 1996. Toxicokinetics of p-tert-octylphenol in male Wistar rats. Arch. Toxicol., 71:112-22 https://doi.org/10.1007/s002040050365
  16. Charpentier AH, Bednarek AK, Daniel RL, Hawkins KA, Laflin KJ, Gaddis S, MacLeod MC and Aldaz CM. 2000. Effects of estrogen on global gene expression: identification of novel targets of estrogen action. Cancer. Res., 60: 5977-5983
  17. Choi KC and Jeung EB. 2003. The biomarker and endocrine disruptors in mammals. In J. Reprod. Dev., 49:337-345 https://doi.org/10.1262/jrd.49.337
  18. Choi SM and Lee BM. 2004. An alternative mode of action of endocrine-disrupting chemicals and chemoprevention. J. Toxicol. Environ. Health. B. Crit. Rev., 7:451-463 https://doi.org/10.1080/10937400490512500
  19. Christakos S, Gabrielides C and Rhoten WB. 1989. Vitamin D-dependent calcium binding proteins: chemistry, distribution, functional considerations, and molecular biology. Endoer. Rev., 10:3-26 https://doi.org/10.1210/edrv-10-1-3
  20. Clark BF. 1971. The effects of oestrogen and progesterone on uterine cell division and epithelial morphology in spayed, adrenalectomized rats. J. Endocrinol., 50:527-528 https://doi.org/10.1677/joe.0.0500527
  21. Dang VH, Choi KC, Hyun SH and Jeung EB. 2007a. Analysis of gene expression profiles in the offspring of rats following maternal exposure to xenoestrogens. Reprod. Toxicol., 23:42-54 https://doi.org/10.1016/j.reprotox.2006.08.010
  22. Dang VH, Choi KC, Hyun SH and Jeung EB. 2007b. Induction of uterine calbindin-D9k through an estrogen receptor-dependent pathway following single injection with xenobiotic agents in immature rats. J. Toxicol. Environ. Health. A., 70:171-182 https://doi.org/10.1080/15287390600755257
  23. Dang VH, Choi KC and Jeung EB. 2007c. Tetrabromodiphenyl Ether (BDE 47) evokes estrogenicity and calbindin-D9k expression through an estrogen receptor-mediated pathway in the uterus of immature rats. Toxicol. Sci., 97: 504-511 https://doi.org/10.1093/toxsci/kfm051
  24. Dang VH, Nguyen TH, Choi KC and Jeung EB. 2007d. A calcium-binding protein, calbindin-D9k, is regulated through an estrogen-receptor-mediated mechanism following xenoestrogen exposure in the GH3 cell line. Toxicol. Sci. In press
  25. Danzo BJ. 1997. Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. Environ. Health. Perspect., 105:294-301 https://doi.org/10.2307/3433266
  26. Darwish HM and DeLuca HF. 1992. Identification of a 1,25dihydroxyvitamin D3-response element in the 5'-flanking region of the rat calbindin D-9k gene. Proc. Natl. Acad. Sci. USA., 89:603-607
  27. Delorme AC, Danan JL and Mathieu H. 1983. Biochemical evidence for the presence of two vitamin D-dependent calcium-binding proteins in mouse kidney. J. Biol. Chem., 258:1878-1884
  28. Dhar DK, Wang TC, Maruyama R, Udagawa J, Kubota H, Fuji T, Tachibana M, Ono T, Otani Hand Nagasue N. 2003. Expression of cytoplasmic TFF2 is a marker of tu-mor metastasis and negative prognostic factor m gastric cancer. Lab. Invest., 83:1343-1352 https://doi.org/10.1097/01.LAB.0000085190.99749.15
  29. Dupret JM, L'Horset F, Perret C, Bernaudin JF and Thomasset M. 1992. Calbindin-D9K gene expression in the lung of the rat. Absence of regulation by 1,25-dihydroxyvitamin D3 and estrogen. Endocrinology, 131 :2643-2648 https://doi.org/10.1210/en.131.6.2643
  30. Elsby R, Maggs JL, Ashby J and Park BK. 2001a. Comparison of the modulatory effects of human and rat liver microsomal metabolism on the estrogenicity of bisphenol A: implications for extrapolation to humans. J. Pharmacol. Exp. Ther., 297:103-113
  31. Elsby R, Maggs JL, Ashby J, Paton D, Sumpter JP and Park BK. 2001b. Assessment of the effects of metabolism on the estrogenic activity of xenoestrogens: A two-stage approach coupling human liver microsomes and a yeast estrogenicity assay. J. Pharmacol. Exp. Ther., 296:329-337
  32. Escriva H, Safi R, Hanni C, Langlois MC, Saumitou-Laprade P, Stehelin D, Capron A, Pierce R and Laudet V. 1997. Ligand binding was acquired during evolution of nuclear receptors. Proc. Natl. Acad. Sci. USA., 94:6803-6808
  33. Francois E, Wang DY, Fulthorpe R, Liss SN and Edwards EA. 2003. DNA microarrays for detecting endocrine-disrupting compounds. Biotechnol. Adv., 22:17-26 https://doi.org/10.1016/j.biotechadv.2003.08.005
  34. Frasor J, Barnett DH, Danes JM, Hess R, Parlow AF and Katzenellenbogen BS. 2003. Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) $\alpha$$\beta$ in the uterus. Endocrinology, 144:3159-3166 https://doi.org/10.1210/en.2002-0143
  35. Fujimoto N, Igarashi K, Kanno J, Honda H and Inoue T. 2004. Identification of estrogen-responsive genes in the GH3 cell line by cDNA microarray analysis. J. Steroid. Biochem. Mol. Biol., 91:121-129 https://doi.org/10.1016/j.jsbmb.2004.02.006
  36. Gaido KW, Leonard LS, Lovell S, Gould JC, Babai D, Portier CJ and McDonnell DP. 1997. Evaluation of chemicals with endocrine modulating activity in a yeast-based steroid hormone receptor gene transcription assay. Toxicol. Appl. Pharmacol., 143:205-212 https://doi.org/10.1006/taap.1996.8069
  37. Galand P, Leroy F and Chretien J. 1971. Effect of oestradiol on cell proliferation and histological changes in the uterus and vagina of mice. J. Endocrinol., 49:243-252 https://doi.org/10.1677/joe.0.0490243
  38. Gardner RM, Verner G, Kirkland JL and Stance! GM. 1989. Regulation of uterine epidermal growth factor (EGF) receptors by estrogen in the mature rat and during the estrous cycle. J. Steroid. Biochem., 32:339-343 https://doi.org/10.1016/0022-4731(89)90205-7
  39. Gorski J, Stormshak F, Harris J and Wertz N. 1977. Hormone regulation of growth: stimulatory and inhibitory influences of estrogens on DNA synthesis. J. Toxicol. Environ. Health., 3:271-279 https://doi.org/10.1080/15287397709529565
  40. Gould JC, Leonard LS, Maness SC, Wagner BL, Conner K, Zacharewski T, Safe S, McDonnell DP and Gaido KW. 1998. Bisphenol A interacts with the estrogen receptor a in a distinct manner from estradiol. Mol. Cell. Endocrinol., 142:203-214 https://doi.org/10.1016/S0303-7207(98)00084-7
  41. Gray LE, 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, Jolmson R, Purdy R, Mihaich E, Safe S and Colborn T. 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. Reprod. Toxicol., 11:719-750 https://doi.org/10.1016/S0890-6238(97)00025-7
  42. Gray LE and Ostby J. 1998. Effects of pesticides and toxic substances on behavioral and morphological reproductive development: endocrine versus nonendocrine mechanisms. Toxicol. Ind. Health., 14:159-184 https://doi.org/10.1177/074823379801400111
  43. Ham KN, Hurley N, Lopata A and Ryan GB 1970. A combined isotopic and electron microscopic study of the response of the rat uterus to exogenous oestradiol. J. Endocrinol., 46:71-8l https://doi.org/10.1677/joe.0.0460071
  44. Hasty LA and Lyttle CR. 1992. Progesterone and RU486 regulation of uterine complement C3 after prior induction with estradiol. Biol, Reprod., 47:285-290 https://doi.org/10.1095/biolreprod47.2.285
  45. Heppell SA, Denslow ND, Folmar LC and Sullivan CV. 1995. Universal assay of vitellogenin as a biomarker for environmental estrogens. Environ. Health. Perspect, 103: Suppl. 7: 9-15 https://doi.org/10.1289/ehp.95103s79
  46. Hong EJ, Choi KC and Jeung EB. 2003. Maternal-fetal transfer of endocrine disruptors in the induction of Calbindin-D9k mRNA and protein during pregnancy in rat model. Mol. Cell. Endocrinol., 212:63-72 https://doi.org/10.1016/j.mce.2003.08.011
  47. Hong EJ, Choi KC and Jeung EB. 2004a. Induction of calbindin-D9k messenger RNA and protein by maternal exposure to alkylphenols during late pregnancy in maternal and neonatal uteri of rats. Biol. Reprod., 71 :669-675 https://doi.org/10.1095/biolreprod.103.026146
  48. Hong EJ, Choi KC, Jung YW, Leung PC and Jeung EB. 2004b. Transfer of maternally injected endocrine disruptors through breast milk during lactation induces neonatal Calbindin-D9k in the rat model. Reprod. Toxicol., 18:661-668 https://doi.org/10.1016/j.reprotox.2004.03.005
  49. Hong EJ, Choi KC and Jeung EB. 2005. Maternal exposure to bisphenol a during late pregnancy resulted in an increase of Calbindin-D9k mRNA and protein in maternal and postnatal rat uteri. J. Reprod. Dev., 51 :499-508 https://doi.org/10.1262/jrd.17012
  50. Hong EJ, Park SH, Choi KC, Leung PC and Jeung EB. 2006. Identification of estrogen-regulated genes by microarray analysis of the uterus of immature rats exposed to endocrine disrupting chemicals. Reprod. Biol. Endocrinol., 4:49 https://doi.org/10.1186/1477-7827-4-49
  51. Hopert AC, Beyer A, Frank K, Strunck E, Wunsche Wand Vollmer G. 1998. Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model. Environ. Health. Perspect., 106:581-586 https://doi.org/10.2307/3434233
  52. Howe RS, Lee YH, Fischkoff SA, Teuscher C and Lyttle CR. 1990. Glucocorticoid and progestin regulation of eosinophil chemotactic factor and complement C3 in the estrogen-treated rat uterus. Endocrinology., 126:3193-3199 https://doi.org/10.1210/endo-126-6-3193
  53. Jefferson WN, Padilla-Banks E and Newbold RR. 2000. Lactoferrin is an estrogen responsive protein in the uterus of mice and rats. Reprod. Toxicol., 14:103-110 https://doi.org/10.1016/S0890-6238(00)00061-7
  54. Jensen Y, Ladekarl M, Holm-Nielsen P, Melsen F and Soerensen FB. 1995. The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer. J. Pathol., 176:343-352 https://doi.org/10.1002/path.1711760405
  55. Jeung EB, Krisinger J, Dann JL and Leung PC. 1992. Molecular cloning of the full-length cDNA encoding the human calbindin-D9k. FEBS. Lett., 307:224-228 https://doi.org/10.1016/0014-5793(92)80772-9
  56. Jeung EB, Leung PC and Krisinger J. 1994. The human calbindin-D9k gene. Complete structure and implications on steroid hormone regulation. J. Mol. Biol., 235: 1231-1238 https://doi.org/10.1006/jmbi.1994.1076
  57. Jones RC and Edgren RA. 1973. The effects of various steroids on the vaginal histology in the rat. Fertil. Steril., 24: 284-291 https://doi.org/10.1016/S0015-0282(16)39613-3
  58. Kirkland JL, LaPointe L, Justin E and Stancel GM. 1979. Effects of estrogen on mitosis in individual cell types of the immature rat uterus. BioI. Reprod., 21 :269-272 https://doi.org/10.1095/biolreprod21.2.269
  59. Korach KS, Chae K, Gibson M and Curtis S. 1991. Estrogen receptor stereochemistry: ligand binding and hormonal responsiveness. Steroids., 56:263-270 https://doi.org/10.1016/0039-128X(91)90045-W
  60. Kos M, O'Brien S, Flouriot G and Gannon F. 2000. Tissuespecific expression of multiple mRNA variants of the mouse estrogen receptor alpha gene. FEBS. Lett., 477:15-20 https://doi.org/10.1016/S0014-5793(00)01750-6
  61. Krisinger J, Dann JL, Currie WD, Jeung EB and Leung PC. 1992. Calbindin-D9k mRNA is tightly regulated during the estrous cycle in the rat uterus. Mol. Cell. Endocrinol., 86: 119-123 https://doi.org/10.1016/0303-7207(92)90182-6
  62. Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S and Gustafsson JA. 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors $\alpha$ and .$\beta$ Endocrinology., 138: 863-870 https://doi.org/10.1210/en.138.3.863
  63. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson Sand Gustafsson JA. 1996. Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. USA., 93: 5925-5930
  64. Kumar R, Wieben E and Beecher SJ. 1989. The molecular cloning of the complementary deoxyribonucleic acid for bovine vitamin D-dependent calcium-binding protein: structure of the full-length protein and evidence for homologies with other calcium-binding proteins of the troponin-C superfamily of proteins. Mol. Endocrinol., 3: 427-432 https://doi.org/10.1210/mend-3-2-427
  65. Laudet V. 1997. Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. J. Mol. Endocrinol., 19:207-226 https://doi.org/10.1677/jme.0.0190207
  66. Laws SC, Carey SA, Ferrell JM, Bodman GJ and Cooper RL. 2000. Estrogenic activity of octylphenol, nonylphenol, bisphenol A and m;thoxychlor in rats. Toxicol. Sci., 54: 154-167 https://doi.org/10.1093/toxsci/54.1.154
  67. Lee GS, Kim HJ, Jung YW, Choi KC and Jeung EB. 2005. Estrogen receptor a pathway is involved in the regulation of Calbindin-D9k in the uterus of immature rats. Toxicol. Sci., 84:270-277 https://doi.org/10.1093/toxsci/kfi072
  68. Leiva MC, Lyttle CR and Jellinck PH. 1991. Complement C3 synthesis, peroxidase activity and eosinophil chemotaxis in the rat uterus: effect of estradiol and testosterone. Mol. Cell. Endocrinol., 81: 105-111 https://doi.org/10.1016/0303-7207(91)90209-B
  69. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P and Evans RM. 1995. The nuclear receptor superfamily: the second decade. Cell., 83:835-839 https://doi.org/10.1016/0092-8674(95)90199-X
  70. Martin L and Finn CA. 1970. Interactions of oestradiol and progestins in the mouse uterus. J. Endocrinol., 48: 109-115 https://doi.org/10.1677/joe.0.0480109
  71. Mathieu CL, Mills SE, Burnett SH, Cloney DL, Bruns DE and Bruns ME. 1989. The presence and estrogen control of immunoreactive calbindin-D9k in the fallopian tube of the rat. Endocrinology., 125:2745-2750 https://doi.org/10.1210/endo-125-5-2745
  72. Miller S, Kennedy D, Thomson J, Han F, Smith R, Ing N, Piedrahita J and Busbee D. 2000. A rapid and sensitive reporter gene that uses green fluorescent protein expression to detect chemicals with estrogenic activity. Toxicol. Sci., 55:69-77 https://doi.org/10.1093/toxsci/55.1.69
  73. Mukku VR and Stancel GM. 1985. Regulation of epidermal growth factor receptor by estrogen. J. Biol, Chem., 260: 9820-9824
  74. Naciff JM, Jump ML, Torontali SM, Carr GJ, Tiesman JP, Overmann GJ and Daston GP. 2002. Gene expression profile induced by 17 alpha-ethynyl estradiol, bisphenol A, and genistein in the developing female reproductive system of the rat. Toxicol. Sci., 68:184-199 https://doi.org/10.1093/toxsci/68.1.184
  75. Nagel SC, vom Saal, FS, Thayer KA, Dhar MG, Boechler M and Welshons WV. 1997. Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ. Health. Perspect., 105 :70-76 https://doi.org/10.2307/3433065
  76. Nelson KG, Takahashi T, Bossert NL, Walmer DK and MeLachlan JA. 1991. Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation. Proc. Natl. Acad. Sci. USA., 88:21-25
  77. Nephew KP, Peters GA and Khan SA. 1995. Cellular localization of estradiol-induced c-fos messenger ribonucleic acid in the rat uterus: c-fos expression and uterine cell proliferation do not correlate strictly. Endocrinology, 136:3007-3015 https://doi.org/10.1210/en.136.7.3007
  78. Nephew KP, Tang M and Khan SA. 1994. Estrogen differentially affects c-jun expression in uterine tissue compartments. Endocrinology, 134:1827-1834 https://doi.org/10.1210/en.134.4.1827
  79. Nguyen TH, Lee GS, Ji YK, Choi KC, Lee CK and Jeung EB. 2005. A calcium binding protein, calbindin-D9k, is mainly regulated by estrogen in the pituitary gland of rats during estrous cycle. Brain. Res. Mol. Brain. Res., 141:166-173 https://doi.org/10.1016/j.molbrainres.2005.09.008
  80. Odum J, Lefevre PA, Tittensor S, Paton D, Routledge EJ, Beresford NA, Sumpter JP and Ashby J. 1997. The rodent uterotrophic assay: critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay. Regul. Toxicol, Pharmacol., 25:176-188 https://doi.org/10.1006/rtph.1997.1100
  81. Owens JW and Ashby J. 2002. Critical review and evaluation of the uterotrophic bioassay for the identification of possible estrogen agonists and antagonists: in support of the validation of the OECD uterotrophic protocols for the laboratory rodent. Organisation for economic co-operation and development. Crit. Rev. Toxicol., 32:445-520 https://doi.org/10.1080/20024091064291
  82. Papaconstantinou AD, Fisher BR, Umbreit TH, Goering PL, Lappas NT and Brown KM. 2001. Effects of beta-estradiol and bisphenol A on heat shock protein levels and localization in the mouse uterus are antagonized by the antiestrogen ICI 182,780. Toxicol, Sci., 63:173-180 https://doi.org/10.1093/toxsci/63.2.173
  83. Ren L, Marquardt MA and Lech JJ. 1997. Estrogenic effects of nonylphenol on pS2, ER and MUCI gene expression in human breast cancer cells-MCF-7. Chem. Biol. Interact., 104:55-64 https://doi.org/10.1016/S0009-2797(97)03767-8
  84. Roche C, Bellaton C, Pansu D, Miller A and Bronner F. 1986. Localization of vitamin D-dependent active $CA^{2+}$ transport in rat duodenum and relation to CaBP. Am. J. Physiol., 251: 0314-320
  85. Roy D, Palangat M, Chen CW, Thomas RD, Colerangle J, Atkinson A and Van ZJ. 1997. Biochemical and molecular changes at the cellular level in response to exposure to environmental estrogen-like chemicals. J. Toxicol. Environ. Health., 50:1-29 https://doi.org/10.1080/009841097160573
  86. Seifert MF, Gray RW and Bruns ME. 1988. Elevated levels of vitamin D-dependent calcium-binding protein (calbindinD9k) in the osteosclerotic (oc) mouse. Endocrinology., 122: 1067-1073 https://doi.org/10.1210/endo-122-3-1067
  87. Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N and Serrano FO. 1995. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ. Health. Perspect., 103: Suppl. 7, 113-122 https://doi.org/10.1289/ehp.95103s7113
  88. Steinmetz R, Brown NG, Allen DL, Bigsby RM and BenJonathan N. 1997. The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. Endocrinology., 138: 1780-1786 https://doi.org/10.1210/en.138.5.1780
  89. Strunck E, Stemmann N, Hopert A, Wunsche W, Frank K and Vollmer G. 2000. Relative binding affinity does not predict biological response to xenoestrogens in rat endometrial adenocarcinoma cells. J. Steroid. Biochem. Mol. Biol., 74: 73-81 https://doi.org/10.1016/S0960-0760(00)00092-3
  90. Sundstrom SA, Komm BS, Ponce-de-Leon H, Yi Z, Teuscher C and Lyttle CR. 1989. Estrogen regulation of tissue-specific expression of complement C3. J. Biol. Chem., 264: 16941-16947
  91. Thornton JW. 2001. Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc. Natl. Acad. Sci. U S A., 98:5671-5676
  92. Tinwell H, Joiner R, Pate I, Soames A, Foster J and Ashby J. 2000. Uterotrophic activity of bisphenol A in the immature mouse. Regul. Toxicol. Pharmacol., 32:118-126 https://doi.org/10.1006/rtph.2000.1412
  93. Tsai RY and McKay RD. 2002. A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes. Dev., 16:2991-3003 https://doi.org/10.1101/gad.55671
  94. Upmeier A, Degen GH, Schuhmacher US, Certa H and Bolt HM. 1999. Toxicokinetics of p-tert-octylphenol in female DA/Han rats after single i.v. and oral application. Arch. Toxicol., 73:217-222 https://doi.org/10.1007/s002040050609
  95. Velardo JT. 1959. Steroid hormones and uterine growth. Ann. N. Y. Acad. Sci., 75:441-462
  96. Wang X, Jones TD, Maclennan GT, Yang XJ, Lopez-Beltran A, Eble JN, Koch MO, Lin H, Baldridge LA, Tretiakova M and Cheng L. 2005. P53 expression in small cell carcinoma of the urinary bladder: biological and prognostic implications. Anticancer. Res., 25:2001-2004
  97. Waring RH and Harris RM. 2005. Endocrine disrupters: a human risk? Mol. Cell. Endocrinol., 244:2-9 https://doi.org/10.1016/j.mce.2005.02.007
  98. Wasserman RH and Fullmer CS. 1989. On the molecular mechanism of intestinal calcium transport. Adv. Exp. Med. Biol., 249:45-65
  99. Watanabe H, Suzuki A, Goto M, Lubahn DB, Handa Hand Iguchi T. 2004. Tissue-specific estrogenic and non-estrogenic effects ofaxenoestrogen, nonylphenol. J. Mol. Endocrinol., 33:243-252 https://doi.org/10.1677/jme.0.0330243
  100. Watanabe H, Suzuki A, Kobayashi M, Takahashi E, Itamoto M, Lubahn DB, Handa H and Iguchi T. 2003. Analysis of temporal changes in the expression of estrogen-regulated genes in the uterus. J. Mol. Endocrinol., 30: 347-358 https://doi.org/10.1677/jme.0.0300347
  101. Watanabe H, Suzuki A, Mizutani T, Khono S, Lubahn DB, Handa H and Iguchi T. 2002. Genome-wide analysis of changes in early gene expression induced by oestrogen. Genes. Cells., 7:497-507 https://doi.org/10.1046/j.1365-2443.2002.00535.x
  102. Watson CS, Bulayeva NN, Wozniak AL and Alyea RA. 2007. Xenoestrogens are potent activators of non genomic estrogenic responses. Steroids, 72:124-134 https://doi.org/10.1016/j.steroids.2006.11.002
  103. Wenger CR, Beardslee S, Owens MA, Pounds G, Oldaker T, Vendely P, Pandian MR, Harrington D, Clark GM and McGuire WL. 1993. DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients. Breast. Cancer. Res. Treat., 28:9-20 https://doi.org/10.1007/BF00666351
  104. White R, Jobling S, Hoare SA, Sumpter JP and Parker MG. 1994. Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology, 135: 175-182 https://doi.org/10.1210/en.135.1.175
  105. Williams K, McKinnell C, Saunders PT, Walker M, Fisher JS, Turner KJ, Atanassova N and Sharpe M. 2001. Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: Evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man. Hum. Reprod. Update., 7:236-247 https://doi.org/10.1093/humupd/7.3.236
  106. Yang HX, Jin GL, Meng L, Zhang JZ, Liu WB and Shou CC. 2005. Screening and identification of proteins interacting with nucleostemin. World. J. Gastroenterol., 11 :4812-4814 https://doi.org/10.3748/wjg.v11.i31.4812