Tamoxifen pp 179-199 | Cite as

Cellular Effects of Early Exposure to Tamoxifen

  • Taisen Iguchi
  • Yasuhiko Ohta


Historically, Tamoxifen has been synthesized as an antiestrogen by Harper and Walpole (1966). However, this substance showed some estrogenic effects when examined in laboratory animals: a complete estrogen agonist in the chick oviduct (Sutherland et al., 1977), a partial agonist with antiestrogenic activity in the immature and ovariectomized rat (Harper and Walpole, 1967; Jordan and Koerner, 1976), and a full agonist in the immature and ovariectomized adult mouse (Harper and Walpole, 1966; Terenius 1971; Jordan et al., 1978; Chou et al., 1992). Two-dimensional electrophoresis revealed that proteins from the vagina of postpuberty Tamoxifen-exposed ovariectomized adult mice showed the same behavior as in those from the vagina of postpubertally estrogenexposed mice, suggesting that Tamoxifen acts as an estrogen agonist (Takamatsu et al., 1992). Tamoxifen can inhibit the estradiol-stimulated increased in uterine wet weight (Harper and Walpole, 1967), however it simultaneously induced hypertrophy of uterine luminal epithelial cells (Kang et al., 1975) and progesterone receptor (PR) synthesis (Dix and Jordan, 1980; Jordan and Gosden, 1982) in rats. Since some human breast tumors are directly dependent on estrogen for growth, Tamoxifen was tested clinically for breast cancer therapy and proved to be at least as effective as other endocrine therapies (Cole et al., 1971; Baum et al., 1995).


Neonatal Exposure Perinatal Exposure Human Endometrial Carcinoma Reprod Toxicol Uterine Luminal Epithelial Cell 
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  1. Anderson M, Storm H and Mouridsen HT (1991): Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early cancer. J Natl Cancer Inst 83:1013–1017CrossRefGoogle Scholar
  2. Anzai Y, Holinka CF, Hirouki K Na Gurpide E (1989): Stimulatory effects of 4-hydroxytamoxifen on proliferation of human endometrial adenocarcinoma cells (Ishikawa line). Cancer Res 49:2362–2365PubMedGoogle Scholar
  3. Arai Y, Mori T, Suzuki Y and Bern HA (1983): Long-term effects of perinatal exposure to sex steroids and diethystilbestrol on the reproductive system of male mammals. Int Rev Cytol 84:235–268PubMedCrossRefGoogle Scholar
  4. Baum M, Brinkley DM, Dossett JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Richards D and Ellis SH (1985): Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer. Lancet 1:836–840Google Scholar
  5. Bern HA (1992a): Diethylstilbestrol (DES) syndrome: present status of animal and human studies. In: Hormonal Carcinogenesis. Li, J, Nandi S, Li SA, eds. Springer-Verlag, New York, pp 1–8Google Scholar
  6. Bigsby RM, Aixin L, Luo K and Cunha GR (1990): Strain differences in the ontogeny of estrogen receptors in murine uterine epithelium. Endocrinology 126:2592–2596PubMedCrossRefGoogle Scholar
  7. Branham WS, Lyn-Cook BD, Andrews A and Sheehan DM (1993b): Growth of separated and recombined neonatal rat uterine luminal epithelium and stroma on extracellular matrix: Effects of in vivo tamoxifen exposure. In Vitro Cell Dev Biol 29A:408–414CrossRefGoogle Scholar
  8. Branham WS, Sheehan DM, Zehr DR, Medlock KL, Nelson CJ and Ridlon E (1985): Inhibition of rat uterine gland genesis by tamoxifen. Endocrinology 117:2238–2248PubMedCrossRefGoogle Scholar
  9. Branham WS, Zehr DR, Chen JJ and Sheehan DM (1988a): Postnatal uterine development in the rat: Estrogen and antiestrogen effects on luminal epithelium. Teratology 38:29–36PubMedCrossRefGoogle Scholar
  10. Branham WS, Zehr DR, Chen JJ and Sheehan DM (1988b): Alterations in developing rat uterine cell populations after neonatal exposure to estrogens and antiestrogens. Teratology 38:271–279PubMedCrossRefGoogle Scholar
  11. Branham WS, Zehr DR and Sheehan D (1993a): Differential sensitivity of rat uterine growth and epithelium hypertrophy to estrogens and antiestrogens. Proc Soc Exp Biol Med 203:297–303PubMedGoogle Scholar
  12. Carson-Jurica MA, Schrader WT and O’Malley BW (1990): Steroid receptor family: structure and functions. Endocr Rev 11:201–220PubMedCrossRefGoogle Scholar
  13. Chamness GC, Bannayan GA, Landry Jr LA, Scheridan PJ and McGuire WL (1979): Abnormal reproductive development in rats after neonatally administered anti-estrogen (tamoxifen). Biol Reprod 21:1087–1090PubMedCrossRefGoogle Scholar
  14. Chiappetta C, Kirkland JL, Loose-Mitchell DS, Murphy L and Stancel GM (1992): Estrogen regulates expression of the jun family of protooncogenes in the uterus. J Steroid Biochem Mol Biol 41:113–123PubMedCrossRefGoogle Scholar
  15. Chou Y-C, Iguchi T and Bern HA (1992): Effects of antiestrogens on adult and neonatal mouse reproductive organs. Reprod Toxicol 6:439–446PubMedCrossRefGoogle Scholar
  16. Cicatiello L, Ambrosino C, Coletta B, Scalona M, Sica V, Bresciani Fand Weisz A (1992): Transcriptional activation of jun and actin genes by estrogen during mitogenic stimulation of rat uterine cells. J Steroid Biochem Mol Biol 41:523–528PubMedCrossRefGoogle Scholar
  17. Clark LL and Satyaswaroop PG (1985): Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma. Cancer Res 45:5417–5420Google Scholar
  18. Cole MP, Jones CTA and Todd IDH (1971): A new anti-oestrogenic agent in late breast cancer. Br J Cancer 25:270–275PubMedCrossRefGoogle Scholar
  19. Colletti RB, Roberts JD, Devlin JT and Copeland KC (1989): Effect of tamoxifen on plasma insulin-like growth factor I in patients with breast cancer. Cancer Res 49:1882–1884PubMedGoogle Scholar
  20. Cunha GR, Taguchi O, Nishizuka Y and Robboy SJ (1987): Teratogenic effects of clomiphene, tamoxifen and diethylstilbestrol on the developing human femal genital tract. Hum Pathol 18:1132–1143PubMedCrossRefGoogle Scholar
  21. DeMuylder X, Neven P, DeSomer M, VanBelle Y, Vanderick G and DeMuylder E (1991): Endometrial lesions in patients undergoing tamoxifen therapy. Int J Gynaecol Obstet 36:127–130CrossRefGoogle Scholar
  22. Dix CJ and Jordan VC (1980): Modulation of rat uterine steroid hormone receptors by estrogen and antiestrogen. Endocrinology 107:2011–2020PubMedCrossRefGoogle Scholar
  23. Dohler K-D, Coquelin A, Davis F, Hines M, Shryne JE and Gorski RA (1984a): Pre- and postnatal influence of testosterone propionate and diethystilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. Brain Res 302:291–295PubMedCrossRefGoogle Scholar
  24. Dohler K-D, Coquelin A, Davis F, Hines M, Shryne JE, Sickmoller PM, Jarzab B and Gorski RA (1986): Pre- and postnatal influence of an estrogen antagonist and an androgen antagonist on differentiation of sexually dimorphic nucleus of the preoptic areas in male and female rats. Neuroendocrinology 42:443–448PubMedCrossRefGoogle Scholar
  25. Dohler K-D, Hines M, Coquelin A, Davis F, Shryne JE and Gorski RA (1982): Pre- and postnatal influence of diethylstilbestrol on differentiation of the sexually dimorphic nucleus in the preoptic area of the female rat brain. Neuroendocr Lett 4:361–365Google Scholar
  26. Dohler K-D, Srivastava SS, Shryne JE, Jarzab B, Sipos A and Gorski RA (1984b): Differentiation of the sexually dimorphic nucleus in the preoptic area of rat brain is inhibited by postnatal treatment with an estrogen antagonist. Neuroendocrinology 38:297–301PubMedCrossRefGoogle Scholar
  27. Fentiman IS, Caleffi M, Rodin A, Murby B and Fogelman I (1989): Bone mineral content of women receiving tamoxifen for mastalgia. Br J Cancer 60:262–264PubMedCrossRefGoogle Scholar
  28. Fornander T, Rutqvist LE, Cedermark BV, Glas U, Mattson A, Silversward JD, Skoog L, Somell A, Theve T, Wilking N, Askergren J and Hjolmar ML (1989): Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1:117–119PubMedCrossRefGoogle Scholar
  29. Forsberg J-G (1969): The development of atypical epithelium in the mouse uterine cervix and vaginal fornix after neonatal oestradiol treatment. Br J Exp Pathol 50:187–195PubMedGoogle Scholar
  30. Forsberg J-G (1979): Development mechanism of estrogen-induced irreversible changes in the mouse cervicovaginal epithelium. Natl Cancer Inst Monogr 51:41–50PubMedGoogle Scholar
  31. Forsberg J-G (1985): Treatment with different antiestrogens in the neonatal period and effects in the cervicovaginal epithelium and ovaries of adult mice: A comparison to estrogen-induced changes. Biol Reprod 32:427–441PubMedCrossRefGoogle Scholar
  32. Furr BJA and Jordan VC (1984): The pharmacology and clinical uses of tamoxifen. Pharmac Ther 25:127–205CrossRefGoogle Scholar
  33. Gal D, Kopel S, Bashevkin M, Lebowitcz L, Lev R and Tancer ML (1991): Oncogenic potential of tamoxifen on endometria of postmenopausal women with breast cancer - preliminary report. Gynecol Oncol 42:120–123PubMedCrossRefGoogle Scholar
  34. Gardner WU (1936): Sexual dimorphism of the pelvis of the mouse, the effect of estrogenic hormones upon the pelvis and upon the development of scrotal hernias. Am J Anat 59:459–483CrossRefGoogle Scholar
  35. Herbst AL and Bern HE (eds) (1981): Developmental Effects of Diethylstilbestrol (DES) in Pregnancy. New York, Thieme-Stratton, pp 203Google Scholar
  36. Herbst AL, Ulfelder H and Poskanzer DC (1971): Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. New Engl J Med 284:878–881PubMedCrossRefGoogle Scholar
  37. Howard E (1959): A complementary action of corticosterone and dehydropiandrosterone on the mouse adrenal, with observations on the reactivity of reproductive tract structures to dehydroepiadrosteroneand 11- hydroxy-androstenedione. Endocrinology 65:785–801PubMedCrossRefGoogle Scholar
  38. Hyder SM, Stancel GM, Nawaz Z, McDonnell DP and Loose-Mitchell DM (1992): Identification of an estrogen response element in the 3’-flanking region of the murine c-fos protooncogene. J Biol Chem 267:18047–18054PubMedGoogle Scholar
  39. Iguchi T (1992): Cellular effects of early exposure to sex hormones and antihormones. lnt Rev Cytol 139:1–57CrossRefGoogle Scholar
  40. Iguchi T and Bern HA (1995): Transgenerational effects: intrauterine exposure to diethylstilbestrol (DES) in humans and the neonatal mouse model. In: Comments on Toxicology, A Soto ed., Gordon and Breach (in press)Google Scholar
  41. Iguchi T, Fukazawa Y and Bern HA (1995): Effects of sex hormones on oncogene expression in vagina and on development of sexual dimorphism of pelvis and anococcygeus muscle in the mouse. Environment Health Perspect (in press)Google Scholar
  42. Iguchi T and Hirokawa ttttt (1986): Changes in male genital organs of mice exposed neonatally to tamoxifen. Proc Japan Acad 62B: 157–160CrossRefGoogle Scholar
  43. Iguchi T, Hirokawa M and Takasugi N (1986a): Occurence of genital tract abnormalities and bladder hernia in female mice exposed neonatally to tamoxi fen. Toxicology 42:1–11PubMedCrossRefGoogle Scholar
  44. Iguchi T, Irisawa S, Fukazawa Y, Uesugi Y and Takasugi N (1989a): Permanent chondrification in the pelvis and occurence of hernias in mice treated neonatally with tamoxifen. Reprod Toxicol 2:127–134CrossRefGoogle Scholar
  45. Iguchi T, Irisawa S, Uesugi Y, Kusunoki S and Takasugi N (1990b): Abnormal development of the os penis in male mice treated neonatally with tamoxifen. Acta Anat 139:201–208PubMedCrossRefGoogle Scholar
  46. Iguchi T, Ostrander PL, Mills KT and Bern HA (1987b): Ovary-independent and ovary-dependent uterine squamous metaplasia in mice induced by neonatal exposure to diethylstilbestrol. Med Sci Res 15:489–490Google Scholar
  47. Iguchi T, Ostrander PL, Mills KT and Bern HA (1988b): Vaginal abnormalities in ovariectomized BALB/cCrgl mice after neonatal exposure to different doses of diethylstilbestrol.Cancer Lett 43:207–214PubMedCrossRefGoogle Scholar
  48. Iguchi T, Takase M and Takasugi N (1986b): Development of vaginal adenosis- like lesions and uterine epithelial stratification in mice exposed perinatally to diethylstilbestrol. Proc Soc Exp Biol Med 181:59–65PubMedGoogle Scholar
  49. Iguchi T, Takase M and Takasugi N (1986c): Persistent anovulation in the ovary of mice treated with human chorionic gonadotropin starting at different early postnatal ages. IRCS Med Sci 14:187–188Google Scholar
  50. Iguchi T, and Takasugi N (1987): Postnatal development of uterine abnormalities in mice exposed to DES in utero. Biol Neonate 52:97–103PubMedGoogle Scholar
  51. Iguchi T, Takei T, Takase M and Takasugi N (1986e): Estrogen participation in induction of cervicovaginal adenosis-like lesions in immature mice exposed prenatally to diethylstilbestrol. Acta Anat 127:110–114PubMedCrossRefGoogle Scholar
  52. Iguchi T, Todoroki R, Yamaguchi S and Takasugi N (1989b): Changes in the uterus and vagina of mice treated neonatally with antiestrogens. Acta Anat 136:146–154PubMedCrossRefGoogle Scholar
  53. Irisawa S and Iguchi T (1990): Critical period of induction by tamoxifen of genital organ abnormalities in female mice. In Vivo 4:175–180PubMedGoogle Scholar
  54. Irisawa S, Iguchi T and Takasugi N (1990): Critical period of induction by tamoxifen of genital organ abnormalities in male mice. Zool Sci 6:541–545Google Scholar
  55. Ismail SM (1994): Pathology of endometrium treated with tamoxifen. J Clin Pathol 47:827–833PubMedCrossRefGoogle Scholar
  56. Jacobson CD, Csernus VJ, Shryne JE and Gorski RA (1981): The influence of gonadectomy, androgen exposure, or a gonadal graft in the neonatal rat on the volume of the sexually dimorphic nucleus of the preoptic area. J Neurosci 1:1142–1147PubMedGoogle Scholar
  57. Jordan VC (1990): Long-term adjuvant tamoxifen therapy for breast cancer. Breast Cancer Res Treat 15:125–136PubMedCrossRefGoogle Scholar
  58. Jordan VC (1992): The role of tamoxifen in the treatment and prevention of breast cancer. Curr Problems Cancer 16:134–176CrossRefGoogle Scholar
  59. Jordan VC (1993): Growth factor regulation by tamoxifen is demonstrated in patients with breast cancer.Cancer 72:1–2PubMedCrossRefGoogle Scholar
  60. Jordan VC, Dix CJ, Naylor KE, Prestwich G and Rowsby L (1978): Nonsteroidal antiestrogens: Their biological effects and potential mechanisms of action. J Toxicol Environ 4:364–390Google Scholar
  61. Jordan VC and Gosden B (1982): Importance of the alkylaminoethoxy side- chain for the estrogenic and antiestrogen actions of tamoxifen and trioxifen in the immature rat uterus. Mol Cell Endocrinol 7:291–306CrossRefGoogle Scholar
  62. Jordan VC and Koerner S (1976): Tamoxifen as an antitumour agent: role of oestradiol and prolactin. J Endocrinol 68:305–310PubMedCrossRefGoogle Scholar
  63. Jordan VC and Murphy CS (1990): Endocrine pharmacology of antiestrogens as antitumor agents. Endocr Rev 11:578–610PubMedCrossRefGoogle Scholar
  64. Jordan VC, Phelps EL and Lindgren JU (1987): Effects of antiestrogens on bone in castrated and intact female rats. Breast Cancer Res Treat 10:3135CrossRefGoogle Scholar
  65. Kamiya K, Sato T, Nishimura N, Goto Y, Kano K and Iguchi T (1995): Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or without postpuberal estrogen administration. Exp Clin Endocrinol (in press)Google Scholar
  66. Kang YH, Anderson WA and DeSombre ER (1975): Modulation of uterine morphology and growth by estradiol- 17ft and estrogen antagonist.J Cell Biol 64:682–691PubMedCrossRefGoogle Scholar
  67. Kincle FA (1990): Hormones and Toxicity in the Neonate. pp 334, SpringerVerlag, BerlinGoogle Scholar
  68. Kirkland JL, Murphy L and Stancel GM (1993): Tamoxifen stimulates expression of the c-fos proto-oncogene in rodent uterus. Mol Pharmacol 43:709–714PubMedGoogle Scholar
  69. Korach KS, Horigome T, Tomooka Y, Yamashita S, Newbold RR and McLachlan (1988): Immunodetection of estrogen receptor in epithelial and stromal tissues of neonatal mouse uterus. Proc Natl Acad Sci USA 85:3334–3337PubMedCrossRefGoogle Scholar
  70. Lecerf F, Nguyen B-L and Pasqualini JR (1988): Biological effects and ultras true tural alterations of cis-tamoxifen, N-desmethyl tamoxifen and 4-hydroxytamoxifen in the uterus and vagina of newborn guinea pigs. Acta Endocrinol 119:85–90PubMedGoogle Scholar
  71. Le Roy X, Escot C, Brouillet J-P, Theillet C, Maudelonde T, Simony-Lafontaine J, Pujol H and Rochefort H (1991): Decrease of o-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer. Oncogene 6:431–437PubMedGoogle Scholar
  72. Loose-Mitchell DS, Chiappetta C and Stancel GM (1988): Estrogen-regulation of c-fos messenger ribonucleic acid. Mol Endocrinol 2:946–951PubMedCrossRefGoogle Scholar
  73. Malfetano JH (1990): Tamoxifen-associated endometrial carcinoma in postmenopausal breast cancer patients. Gynecol Oncol 39:82–84PubMedCrossRefGoogle Scholar
  74. Mori T and Nagasawa, H (eds) (1988): Toxicity of Hormones in Perinatal Life. p. 184, Boca Raton, Florida, CRC PressGoogle Scholar
  75. Nephew KP, Polek TC, Akcali KC and Khan SA (1993): The antiestrogen tamoxifen induces c-fos and jun-B, but not c-jun or jun-D, protooncogenes in the rat uterus. Br Med J 309:1313–1314Google Scholar
  76. Newbold RR and McLachlan JA (1982): Vaginal adenosis and adenocarcinoma in mice exposed prenatally or neonatally to diethylstilbestrol. Cancer Res 42:2003–2011PubMedGoogle Scholar
  77. Newbold RR and McLachlan J A (1988): Neoplastic and non-neoplastic lesions in male reproductive organs following perinatal exposure to hormones and related substances. In: Toxicity of Hormones in Perinatal Life. Mori T and Nagasawa H (eds), CRC Press, Boca Raton, Florida, pp 89–109Google Scholar
  78. Nguyen BL, Giambiagi N, May rand C, Lecerf F and Pasqualini JR (1986): Estrogen and progesterone receptors in the fetal and newborn vagina of guinea pig: Biological, morphological and ultrastructural responses to tamoxifen and estradiol. Endocrinology 119:978–988PubMedCrossRefGoogle Scholar
  79. Nishimura N, Goto Y and Iguchi T (1993): Tamoxifen induces expressions of oncogenes and estrogen receptor in genital tracts of female mice. Zool Sci Suppl 10:128Google Scholar
  80. Noguchi S, Motomura K, Inaji H, Imaoka S and Koyama H (1993): Down- regulation of transforming growth factor-alpha by tamoxifen in human breast cancer. Cancer 72:131–136PubMedCrossRefGoogle Scholar
  81. Ohta Y (1982): Deciduoma formation in rats ovariectomized at different ages. Biol Reprod 27:303–311CrossRefGoogle Scholar
  82. Ohta Y (1985): Deciduomal response in prepubertal rats adrenalectomized- ovariectomized at different ages of early postnatal life. Zool Sci 2:89–93Google Scholar
  83. Ohta Y (1995): Sterility in neonatally androgenized female rats and the decidual cell reaction, lnt Rev Cytol 160:1–52CrossRefGoogle Scholar
  84. Ohta Y, Iguchi T and Takasugi N (1989): Deciduoma formation in rats treated neonatally with the anti-estrogens tamoxifen and MER-25.Reprod Toxicol 3:207–212PubMedCrossRefGoogle Scholar
  85. Ohta Y and Takasugi N (1974): Ultrastructural changes in the testis of mice given neonatal injections of estrogen. Endocrinol Japan 21:183–190Google Scholar
  86. Ostrander PL, Mills KT and Bern HA (1985): Long-term responses of the mouse uterus to neontal diethylstilbestrol treatment and to later sex hormone exposure. J Natl Cancer Inst 74:121–135PubMedGoogle Scholar
  87. Pasqualini JR and LEcerf F (1986): Ultrastructural modifications provokes by tamoxifen either along or combined with oestradiol in the uteri of fetal or newborn guinea-pigs.J Endocrinol 110:197–202PubMedCrossRefGoogle Scholar
  88. Pasqualini JR, Nguyen B-L, Mayrand C and Lecerf F (1986a): Oestrogen agonistic effects of tamoxifen in the uterus of newborn guinea pigs after short and long treatment. Biological and histological studies. Acta Endocrinol 111:378–386PubMedGoogle Scholar
  89. Pasqualini JR, Nguyen B-L, Sumida C, Giambiagi N and Mayrand C (1986b): Tamoxifen and progesterone effects in target tissues during the perinatal period. J Steroid Biochem 25:853–857PubMedCrossRefGoogle Scholar
  90. Plapinger L (1982): Surface morphology of uterine and vaginal epithelia in mice during normal postnatal development.Biol Reprod 26:961–972PubMedCrossRefGoogle Scholar
  91. Plapinger L and Bern HA (1979): Adenosis-like lesions and other cervicovaginal abnormalities in mice treated perinatally with estrogen. J Natl Cancer Inst 63:507–518PubMedGoogle Scholar
  92. Pollak M, Costantino J, Blauer S-A, Guy da H, Redmond C, Fisher B and Margolese R (1990): Effect of tamoxifen on serum insulin-like growth factor I levels in stage I breast cancer patients. J Natl Cancer Inst 82:1693–1697PubMedCrossRefGoogle Scholar
  93. Sakakibara K, Kan NC and Satyaswaroop PG (1992): Both 1713-estradiol and tamoxifen induce c-fos messenger ribonucleic acid expression in human endometrial carcinoma grown in nude mice. Am J Obstet Gynecol 166:206–212PubMedGoogle Scholar
  94. Sato T, Chiba A, Hayashi S, Okamura H, Ohta Y, Takasugi N and Iguchi T (1994a): Induction of estrogen receptor and cell division in genital tracts of male mice by neonatal exposure to diethylstilbestrol.Reprod Toxicol 8:145–153PubMedCrossRefGoogle Scholar
  95. Sato T, Ohta Y, Okamura H, Hayashi S and Iguchi T (1994b): Estrogen receptor mRNA expression in the genital tract of female mice by estrogen (DES) and antiestrogen (tamoxifen). Zool Sci Suppl 11:17Google Scholar
  96. Sato T, Okamura H, Ohta Y, Hayashi S, Takamatsu Y, Takasugi N and Iguchi T (1992): Estrogen receptor expression in the genital tract of female mice treated neonatally with diethylstilbestrol. In Vivo 6:151–156PubMedGoogle Scholar
  97. Satyaswaroop PG, Zaino RJ and Mortel R (1984): Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice. Cancer Res 44:4006–4010PubMedGoogle Scholar
  98. Selye H, Collip JB and Thomson DL (1933): On the effect of the anterior pituitary-like hormone on the ovary of the hypophysectomized rat. Endocrinology 17:494–500CrossRefGoogle Scholar
  99. Sutherland RL, Mester J and Baulien EE (1977): Tamoxifen is a potent ‘pure’ antiestrogen in chick oviduct. Nature 267:434–435PubMedCrossRefGoogle Scholar
  100. Taguchi O (1987): Reproductive tract lesions in male mice treated neonatally with tamoxifen. Biol Reprod 37:113–116PubMedCrossRefGoogle Scholar
  101. Taguchi O and Nishizuka Y (1985): Reproductive tract abnormalities in female mice treated neonatally with tamoxifen. Am J Obstet Gynecol 151:675–678PubMedGoogle Scholar
  102. Takamatsu Y, Iguchi T and Takasugi N (1992): Effects of postpubertal treatment with diethylstilbestrol and tamoxifen on protein expression in the vagina and uterus of neonatally diethylstilbestrol-exposed mice. In Vivo 6:271–278PubMedGoogle Scholar
  103. Takano-Yamamoto T and Rodan GA (1990): Direct effects of 17B-estradiol on trabecular bone in ovariectomized rats. Proc Natl Acad Sci USA 87:2172–2176PubMedCrossRefGoogle Scholar
  104. Takasugi N (1963): Vaginal cornification in persistent-estrous mice. Endocrinology 72:607–619PubMedCrossRefGoogle Scholar
  105. Takasugi N (1976): Cytological basis for permanent vaginal changes in mice treated neonatally with steroid hormones. Int Rev Cytol 44:193–224PubMedCrossRefGoogle Scholar
  106. Takasugi N (1979): Development of permanently proliferated and cornified vaginal epithelium in mice treated neonatally with steroid hormones and the implication in tumorigenesis.Natl Cancer Inst Monogr 51:57–66PubMedGoogle Scholar
  107. Takasugi N, Bern HA and DeOme KB (1962): Persistent vaginal coraification in mice. Science 138:438–439PubMedCrossRefGoogle Scholar
  108. Terenius L (1971): Structure-activity relationships of anti-oestrogens with regard to interaction with 17ft-oestradiol in the mouse uterus and vagina. Acta Endocrinol Suppl 66:431 -447Google Scholar
  109. Turner RT, Colvard DS and Spelsberg TC (1990): Estrogen inhibition of peiosteal bone formation in rat long bones: down-regulation of gene expression for bone matrix proteins. Endocrinology 127:1346–1351PubMedCrossRefGoogle Scholar
  110. Turner RT, Riggs BL and Spelsberg TC (1994): Skeletal effects of estrogen. Endocr Rev 15:275–300PubMedGoogle Scholar
  111. Turner RT, Wakley GK, Hannon KS and Bell NH (1987): Tamoxifen prevents the skeletal effects of ovarian hormone deficiency in rats. J Bone Min Res 2:449–456CrossRefGoogle Scholar
  112. Turner RT, Wakley GK, Hannon KS and Bell NH (1988): Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone deficient rats. Endocrinology 122:1146–1150PubMedCrossRefGoogle Scholar
  113. Uesugi Y, Ohta Y, Asashima M and Iguchi T (1992a): Comparative study of sexual dimorphism of the innominate bone in rodents and amphibians. Anat Rec 234:432–437PubMedCrossRefGoogle Scholar
  114. Uesugi Y, Taguchi O, Noumura T and Iguchi T (1992b): Effects of steroids on the development of sexual dimorphism in mouse innominate bone. Anat Rec 234:541–548PubMedCrossRefGoogle Scholar
  115. Uesugi Y, Sato T and Iguchi T (1993): Morphometric analysis of the pelvis in mice treated neonatally with tamoxifen. Anat Rec 235:126–130PubMedCrossRefGoogle Scholar
  116. Webb DK, Moulton BC and Kahn SA (1991): Estrogen induced expression of the c-jun protooncogene in the mature and immature rat uterus. Biochem Biophys Res Commun 175:480–485CrossRefGoogle Scholar
  117. Weisz A and Bresciani F (1988): Estrogen induces expression of c-fos and c- myc protooncogenes in rat uterus. Mol Endocrinol 2:816–824PubMedCrossRefGoogle Scholar
  118. Weisz A, Cicatiello L, Persico M and Bresciani F (1990): Estrogen stimulated transcription of c-jun proto-oncogene. Mol Endocrinol 4:1041–1050PubMedCrossRefGoogle Scholar
  119. Weisz A and Rosales R (1990): Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor. Nucleic Acids Res 18:5097–5106PubMedCrossRefGoogle Scholar
  120. Yamashita S, Newbold RR, McLachlan JA and Korach KS (1989): Development pattern of estrogen receptor expression in female mouse genital tracts. Endocrinology 125:2888–2896PubMedCrossRefGoogle Scholar
  121. Yamashita S, Newbold RR, McLachlan JA and Korach KS (1990): The role of estrogen receptor in uterine epithelial proliferation and cytodifferentiation in neonatal mice.Endocrinology 127:2456–2463PubMedCrossRefGoogle Scholar

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© Birkhäuser Boston 1996

Authors and Affiliations

  • Taisen Iguchi
  • Yasuhiko Ohta

There are no affiliations available

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