Skip to main content
SpringerLink
Log in
Book cover

Cell Death in Reproductive Physiology pp 272–291Cite as

Synthetic Estrogen-Mediated Alterations in Uterine Cell Fate

  • Chapter

Part of the book series: Proceedings in the Serono Symposia USA Series ((SERONOSYMP))

Abstract

Our experimental system is uniquely suited to the pursuit of two complementary objectives: first, delineation of the mechanisms whereby estrogens regulate uterine growth and morphogenesis, and second, identification of mechanistic alterations that cause degeneration of the normal growth process to the unregulated neoplastic state. These are biomedically important issues because: first, successful conception and gestation demands normal uterine form and function, and second, estrogen-dependent uterine neoplasms are responsible for considerable morbidity and mortality. Since estrogens normally elicit a striking, yet ultimately limited, growth response in the mature mammalian uterus, a well-integrated interplay of positive and negative regulatory pathways must be involved. To probe this topic, we have exploited a model of atypical estrogen responsiveness that reflects lesions in such regulatory pathways.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Herbst AL, Scully RE, Robboy SJ. Prenatal diethylstilbestrol exposure and human genital tract abnormalities. Monogr Natl Cancer Inst 1979; 51: 25–35.

    Google Scholar 

  2. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 1971; 284: 878–81.

    Article  PubMed  CAS  Google Scholar 

  3. Marselos M, Tomatis L. Diethylstilbestrol: I. Pharmacology, toxicology and carcinogenicity in humans. Eur J Cancer 1992;28A: 1182–9.

    Article  PubMed  CAS  Google Scholar 

  4. Marselos M, Tomatis L. Diethylstilbestrol: II. Pharmacology, toxicology and carcinogenicity in experimental animals. Eur J Cancer 1993;29A:149–55.

    Article  Google Scholar 

  5. Leavitt WW, Evans RW, Hendry WJ. Etiology of DES-induced uterine tumors in the Syrian hamster. In: Leavitt WW, ed. Hormones and Cancer. New York: Plenum Publishing Corporation, 1982: 63–86.

    Chapter  Google Scholar 

  6. Evans RW, Chen TJ, Hendry WJ, Leavitt WW. Progesterone regulation of estrogen receptor in the hamster uterus during the estrous cycle. Endocrinology 1984; 107: 383–90.

    Article  Google Scholar 

  7. Hendry WJ, Leavitt WW. Binding and retention of estrogen in the uterus of hamsters treated neonatally with diethylstilbestrol. J Steroid Biochem 1982; 17: 479–87.

    Article  PubMed  CAS  Google Scholar 

  8. Hendry WJ, Branham WS, Sheehan DM. The hamster cheek pouch as a convenient ectopic site for studies of uterine morphogenesis and endocrine responsiveness. Differentiation 1992; 51: 49–54.

    Article  PubMed  Google Scholar 

  9. Hendry WJ, Leavitt WW. Altered morphogenesis of the immature hamster uterus following neonatal exposure to diethylstilbestrol. Differentiation 1993; 52: 221–7.

    Article  PubMed  CAS  Google Scholar 

  10. Newbold RR, Bullock BC, McLachlan JA. Diverticulosis and salpingitis isthmica nodosa (SIN) of the fallopian tube. Am J Pathol 1984; 117: 333–5.

    PubMed  CAS  Google Scholar 

  11. Saunders FJ. Effects of sex steroids and related compounds on pregnancy and on the development of the young. Physiol Rev 1968; 48: 601–43.

    PubMed  CAS  Google Scholar 

  12. Sandow BA, West NB, Norman RL, Brenner RM. Hormonal control of apoptosis in hamster uterine luminal epithelium. Am J Anat 1979; 156: 15–36.

    Article  PubMed  CAS  Google Scholar 

  13. Terada N, Yammamoto R, Takada T, et al. Inhibitory effect of progesterone on cell death of mouse uterine epithelium. J Steroid Biochem 1989; 33: 1091–6.

    Article  PubMed  CAS  Google Scholar 

  14. Pollard JW, Pacey J, Cheng SVY, Jordan EG. Estrogens and cell death in murine luminal epithelium. Cell Tissue Res 1987; 249: 533–40.

    Article  PubMed  CAS  Google Scholar 

  15. Nawaz S, Lynch MP, Galand P, Gerschenson LE. Hormonal regulation of cell death in rabbit uterine epithelium. Am J Pathol 1987; 127: 51–9.

    PubMed  CAS  Google Scholar 

  16. Rotello RJ, Hocker MB, Gerschenson LE. Biochemical evidence for programmed cell death in rabbit uterine epithelium. Am J Pathol 1989; 134: 491–5.

    PubMed  CAS  Google Scholar 

  17. Schwartzman RA, Cidlowski JA. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev 1993; 14: l33–51.

    Google Scholar 

  18. Gavrieli Y, Sherman Y, Ben-Sasson A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992; 119: 493–501.

    Article  PubMed  CAS  Google Scholar 

  19. Stack G, Gorski J. Direct mitogenic effect of estrogen on the prepuberal rat uterus: studies on isolated nuclei. Endocrinology 1984; 115: 1141–50.

    Article  PubMed  CAS  Google Scholar 

  20. Holinka CF. Proliferation and responsiveness to estrogen of human endometrial cancer cells under serum-free culture conditions. Cancer Res 1989; 49: 3297–301.

    PubMed  CAS  Google Scholar 

  21. Silberstein GB, Horn KV, Shyamala G, Daniel CW. Essential role of endogenous estrogen in directly stimulating mammary growth demonstrated by implants containing pure antiestrogens. Endocrinology 1994; 134: 84–90.

    Article  PubMed  CAS  Google Scholar 

  22. Shafie SM. Estrogen and the growth of breast cancer: new evidence suggests indirect action. Science 1980; 209: 701–2.

    Article  PubMed  CAS  Google Scholar 

  23. Richards J, Imagawa W, Balakrishnan A, Edery M, Nandi S. The lack of effect of phenol red or estradiol on the growth response of human, rat, and mouse mammary cells in primary culture. Endocrinology 1988; 123: 1335–40.

    Article  PubMed  CAS  Google Scholar 

  24. Alkhalaf M, Propper AY, Adessi GL. Proliferation of guinea pig uterine epithelial cells in serum-free culture conditions: effect of 17-β estradiol, epidermal growth factor and insulin. J Steroid Biochem Mol Biol 1991; 38: 345–50.

    Article  PubMed  CAS  Google Scholar 

  25. Gardner RM, Kirkland JL, Ireland JS, Stancel G. Regulation of the uterine response to estrogen by thyroid hormone. Endocrinology 1978; 103: 1164–72.

    Article  PubMed  CAS  Google Scholar 

  26. Lippman ME, Dickson RB, Gelmann EP, et al. Growth regulation of human breast carcinoma occurs through regulated growth factor secretion. J Cell Biochem 1987; 35: 1–16.

    Article  PubMed  CAS  Google Scholar 

  27. Ignar-Trowbridge DM, Nelson KG, Bidwell MC, et al. Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor. Proc Natl Acad Sci USA 1992: 4658–62.

    Google Scholar 

  28. Mizejewski GJ, Vonnegut M, Jacobson HI. Estradiol-activated á-fetoprotein suppresses the uterotropic response to estrogens. Proc Natl Acad Sci USA 1983; 80: 2733–7.

    Article  PubMed  CAS  Google Scholar 

  29. Soto AM, Sonnenschein C. Cell proliferation of estrogen-sensitive cells: the case for negative control. Endocr Rev 1987; 8: 44–52.

    Article  PubMed  CAS  Google Scholar 

  30. Knabbe C, Lippman ME, Wakefield LM, et al. Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human breast cancer cells. Cell 1987; 48: 417–28.

    Article  PubMed  CAS  Google Scholar 

  31. DiAugustine RP, Petruez P, Bell GI, et al. Influences of estrogens on mouse uterine epidermal growth factor precursor protein and messenger ribonucleic acid. Endocrinology 1988; 122: 2355–63.

    Article  PubMed  CAS  Google Scholar 

  32. Gardner RM, Verner G, Kirkland JL, Stancel GM. Regulation of uterine epidermal growth factor (EGF) receptors by estrogen in the mature rat and during the estrous cycle. J Steroid Biochem 1989; 32: 339–43.

    Article  PubMed  CAS  Google Scholar 

  33. Murphy LJ, Ghahary A. Uterine insulin-like growth factor: regulation of expression and its role in estrogen-induced uterine proliferation. Endocr Rev 1990; 11: 443–53.

    Article  PubMed  CAS  Google Scholar 

  34. Weisz A, Cicatiello L, Persico E, Scaloma M, Bresciani F. Estrogen stimulates transcription of c-jun protooncogene. Mol Endocrinol 1990; 4: 1041–50.

    Article  PubMed  CAS  Google Scholar 

  35. Chiappetta C, Kirkland JL, Loose-Michell DS, Murthy L, Stancel GM. Estrogen regulates expression of the jun family of protooncogenes in the uterus. J Steroid Biochem Moir Biol 1992; 41: 113 23.

    Google Scholar 

  36. Loose-Mitchell DS, Chiappeta C, Stancel GM. Estrogen regulation of c-fos messenger ribonucleic acid. Mol Endocrinol 1988; 2: 946–51.

    Article  PubMed  CAS  Google Scholar 

  37. Jouvenot M, Pellerin I, Alkhalaf M, Marechal G, Royez M, Adessi GL. Effects of 17 beta-estradiol and growth factors on c-fos gene expression in endometrial epithelial cells in primary culture. Mol Cell Endocrinol 1990; 72: 149–57.

    Article  PubMed  CAS  Google Scholar 

  38. Lau LF, Nathans D. Expression of a set of growth-related immediate early genes in BALE/c 3T3 cells: coordinate regulation with c-fos or c-rye. Proc Natl Acad Sci USA l987;84:l182–6

    Article  PubMed  CAS  Google Scholar 

  39. Luscher B, Eisenman RN. New light on Myc and Myb. Part 1. Myc. Genes Dev 1990; 4: 2025–35.

    Article  CAS  Google Scholar 

  40. Colotta F, Polentarutti N, Sironi M, Mantovani A. Expression and involvement of c-fos and c-jun protooncogenes in programmed cell death induced by growth factor deprivation in lymphoid cell lines. J Biol Chem 1992; 267: 18278–83.

    PubMed  CAS  Google Scholar 

  41. Williams GT, Smith CA. Molecular regulation of apoptosis: genetic controls on cell death. Cell 1993; 74: 777–9.

    Article  PubMed  CAS  Google Scholar 

  42. Hermeking H, Eick D. Mediation of c-Myc-induced apoptosis by p53. Science 1994; 265: 2091–3.

    Article  PubMed  CAS  Google Scholar 

  43. Gewirtz DA. DNA damage, gene expression, growth arrest and cell death. Oncol Res 1993; 5: 397–408.

    PubMed  CAS  Google Scholar 

  44. Ueda N, Shah SV. Apoptosis. J Lab Clin Med 1994; 124: 169–77.

    CAS  Google Scholar 

  45. Hockenbery DM, Zutter M, Richey W, Nahm M, Korsmeyer SJ. Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci USA. 1991; 88: 6961–5.

    Article  PubMed  CAS  Google Scholar 

  46. Boise LH, Gonzalez-Garcia M, Postema CE, et al. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993; 74: 597–608.

    Article  PubMed  CAS  Google Scholar 

  47. Yang E, Zha J, Jockei J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2 displaces Bax and promotes cell death. Cell 1995; 80: 285–91.

    Article  PubMed  CAS  Google Scholar 

  48. Oltvai Z, Milliman C, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609–19.

    Article  PubMed  CAS  Google Scholar 

  49. Barinaga M. Cell suicide: by ICE, not fire. Science 1994; 263: 754–6.

    Article  PubMed  CAS  Google Scholar 

  50. Rotello RJ, Lieberman RC, Purchio AF, Gerschenson LE. Coordinated regulation of apoptosis and cell proliferation by transforming growth factor βl in cultured uterine epithelial cells. Proc Natl Acad Sci USA 1991; 88: 3412–5.

    Article  PubMed  CAS  Google Scholar 

  51. Moulton BC. Transforming growth factor-β stimulates endometrial stromal apoptosis in vitro. Endocrinology 1994; 134: 1055–60.

    Article  PubMed  CAS  Google Scholar 

  52. Bursch W, Oberhammer F, Jirtle RL, et al. Transforming growth factor-β1 as a signal for induction of cell death by apoptosis. Br J Cancer 1993; 67: 531–6.

    Article  PubMed  CAS  Google Scholar 

  53. Elovic A, Galli SJ, Weller P, et al. Production of transforming growth factor alpha by hamster eosinophils. Am J Pathol 1990; 137: 1425–34.

    PubMed  CAS  Google Scholar 

  54. Chiang T, McBride J, Chou MY, Nishimura I, Wong DTW. Molecular cloning of the complementary DNA coding for the hamster TGF-a mature peptide. Carcinogenesis 1991; 12: 529–32.

    Article  PubMed  CAS  Google Scholar 

  55. Ghiabi M, Gallagher GT, Wong DTW. Eosinophils, tissue eosinophilia, and eosinophil-derived transforming growth factor á in hamster oral carcinogenesis. Cancer Res 1992; 52: 389–93.

    PubMed  CAS  Google Scholar 

  56. Vogt PK, Bos TJ. jun: oncogene and transcription factor. Adv Cancer Res 1990; 55: 1–35.

    Article  PubMed  CAS  Google Scholar 

  57. Distel RJ, Spiegelman BM. Protooncogene c-fos as a transcription factor. Adv Cancer Res 1990; 55: 37–55.

    Article  PubMed  CAS  Google Scholar 

  58. Koskinen PJ, Alitalo K. Role of myc amplification and overexpression in cell growth, differentiation and death. Semin Cancer Biol 1993; 4: 3–12.

    PubMed  CAS  Google Scholar 

  59. Lithgow T, van Driel R, Bertram JF, Strasser A. The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum, and the outer mitochondria) membrane. Cell Growth Differ 1994; 5: 411–7.

    PubMed  CAS  Google Scholar 

  60. Krajewski S, Tanaka S, Takayama S, Schibler MJ, Fenton W, Reed JC. Investigation of the subcellular distribution of the Bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondria) membrane. Cancer Res 1993; 53: 4701–14.

    PubMed  CAS  Google Scholar 

  61. Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol 1994; 145: 1323–36.

    PubMed  CAS  Google Scholar 

  62. Krajewski S, Krajewski M, Shabaik A, et al Immunohistochemical analysis of in vivo patterns of Bcl-X expression. Cancer Res 1994; 54: 5501–7.

    PubMed  CAS  Google Scholar 

  63. Wyllie AH. Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview. Cancer Metastasis Rev 1992; 11: 95–103.

    Article  PubMed  CAS  Google Scholar 

  64. Kerr JF, Winterford CM, Harmon BV. Apoptosis: its significance in cancer and cancer therapy. Cancer 1993; 73: 2013–26.

    Article  Google Scholar 

  65. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456–62.

    Article  PubMed  CAS  Google Scholar 

  66. Preston GA, Lang JE, Maronpot RR, Barret JC. Regulation of apoptosis by low serum in cells of different stages of neoplastic progression: enhanced susceptibility after loss of a senescence gene and decreased susceptibility after loss of a tumor suppressor gene. Cancer Res 1994; 54: 4214–23.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. William J. Hendry III
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinglong Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wendell W. Leavitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William S. Branham
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel M. Sheehan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA, 02114, USA

    Jonathan L. Tilly Ph.D.

  2. Center for Research on Reproduction and Women’s Health, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA

    Jerome F. Strauss III M.D., Ph.D.

  3. W. Alton Jones Cell Science Center, Lake Placid, NY, 12946, USA

    Martin Tenniswood Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Hendry, W.J., Zheng, X., Leavitt, W.W., Branham, W.S., Sheehan, D.M. (1997). Synthetic Estrogen-Mediated Alterations in Uterine Cell Fate. In: Tilly, J.L., Strauss, J.F., Tenniswood, M. (eds) Cell Death in Reproductive Physiology. Proceedings in the Serono Symposia USA Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-1944-6_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-1944-6_20

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7351-6

  • Online ISBN: 978-1-4612-1944-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation