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Altered Estrogen Action in the Senescent Rat Uterus: A Model for Steroid Resistance during Aging

  • George S. Roth
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 196)

Abstract

The estrogen stimulated rat uterus serves as a useful model to examine steroid resistance during aging. This system exhibits receptor loss, impaired stimulation of RNA polymerase II and defects in nuclear translocation (or enhanced association) of receptor-estradiol complexes. All of these defects appear to contribute in part to decreased estrogen responsiveness of the senescent rodent uterus.

Keywords

Estrogenic Stimulation Mature Nucleus Cytoplasmic Receptor Receptor Loss Biosynthetic Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    N. W. Shock, The physiology of aging. Scientific American 29: 100 (1962).Google Scholar
  2. 2.
    G. Roth, G. D. Hess, Changes in the mechanisms of hormone and neurotransmitter action during aging: Current status of the role of receptor and post-receptor alterations. Mech. Ageing and Devel. 20: 175 (1982).CrossRefGoogle Scholar
  3. 3.
    R. C. Adelman, G. S. Roth, (eds) Endocrine and Neuroendocrine Mechanisms of Aging, CRC Press, Boca Raton, FL (1982).Google Scholar
  4. 4.
    R. I. Gregerman, E. L. Bierman, Aging and hormones, In: Textbook of Endocrinology (R.H. Williams, ed), pp. 1192–1212, Saunders, Philadelphia (1981).Google Scholar
  5. 5.
    C. F. Holinka, J. F. Nelson, C. E. Finch, Effect of estrogen treatment on estradiol binding capacity in uteri of aged rats. The Gerontologist 15: 30 (1975).Google Scholar
  6. 6.
    S. Saiduddin, H. P. Zassenhaus, Estrus cycles decidualization response and uterine estrogen and progesterone receptor in Fisher 344 virgin aging rats. Proc. Soc. Exp. Biol. and Med. 161: 119 (1979).Google Scholar
  7. 7.
    A. J. W. Hseueh, G. F. Erickson, and K. H. Lu, Changes in uterine estrogen receptor and morphology in aging female rats. Biol. of Repro. 21: 793 (1979).CrossRefGoogle Scholar
  8. 8.
    M. J. Jiang, M. T. Peng, Cytoplasmic and nuclear binding of estradiol in the brain and pituitary of old female rats. Gerontology 27: 51 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    M. S. Gesell, G. S. Roth, Decrease in rat uterine estrogen receptors during aging: physio-and immuno-chemical properties. Endocrinology 109: 1502 (1981).PubMedCrossRefGoogle Scholar
  10. 10.
    R. S. Chuknyiska, M. Haji, R. H. Foote, G. S. Roth, Effect of aging on nuclear association of rat uterine estradiol receptor complexes. Endocrinology 116: 547 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Haji, G. S. Roth, in press, Impaired estrogen stimulation of RNA polymerase II activity in uterine nuclei of senescent rats. Mech. Ageing and Devel. 25:141 (1984).CrossRefGoogle Scholar
  12. 12.
    M. Haji, R. S. Chuknyiska, G. S. Roth, Isolated uterine nuclei and cytosol receptors of aged rats exhibit impaired estrogenic stimulation of RNA polymerase II, Proc. Nat. Acad. Sci., USA. 81: 7481 (1984).CrossRefGoogle Scholar
  13. 13.
    R. L. Singhal, H. R. E. Valadares, G. M. Ling, Estrogenic regulation of uterine carbohydrate metabolism during senescence. Am. J. Physiol. 217: 793 (1969).PubMedGoogle Scholar
  14. 14.
    A. A. Soriero, Autoradiographic study of the effect of estrogen on in vivo incorporation of 3H-uridine into uterine smooth muscle and stromal RNA in the aging ovariectomized mouse. J. Gerontol. 35: 167 (1980).PubMedGoogle Scholar
  15. 15.
    A. A. Soriero, G. B. Talbert, The effect of estrogen on protein and RNA concentration and on de novo synthesis of RNA in the uterus of aging ovariectomized mice. J. Gerontol. 30: 264 (1975).PubMedGoogle Scholar
  16. 16.
    J. F. Nelson, C. F. Holinka, C. E. Finch, Age related changes in estradiol binding capacity of mouse uterine cytosol. Abstr 29th Ann Mtg of the Geront Soc p. 86 (1976).Google Scholar
  17. 17.
    S. Belisle, C. Beaudry, Endocrine aging in CBA mice. Characterization of urine cytosolic and nuclear sex steroid receptors. Exp. Gerontol. 17: 417 (1982).PubMedCrossRefGoogle Scholar
  18. 18.
    W. C. Chang, M. T. Hoopes, G. S. Roth, Biosynthetic rates of proteins having the characteristics of glucocorticoid receptors in adipocytes of mature and senescent rats. J. Gerontol. 36: 386 (1981).PubMedGoogle Scholar
  19. 19.
    J. A. Joseph, C. R. Filburn, G. S. Roth, Development of dopamine receptor denervation supersensitivity in the neostriatum of the senescent rat. Life Sci. 29: 595 (1981).CrossRefGoogle Scholar
  20. 20.
    B. A. Rosner, V. J. Cristofalo, Charges in specific dexamethasone binding during aging in WI-38 cells. Endocrinology 108: 1965 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    J. Pitha, B. A. Hughes, J. W. Kusiak, E. M. Dax, S. P. Baker, Regeneration of beta-adrenergic receptors in senescent rats; study using an irreversible antagonist. Proc. Nat. Acad. Sci. USA 79: 4424 (1982).PubMedCrossRefGoogle Scholar
  22. 22.
    J. M. Henry, G. S. Roth, submitted, Effect of aging on recovery of striatal dopamine receptors following N-erthoxycarbonyl2-ethoxyl, 2-dihydroquinoline (EEDQ) blockade.Google Scholar
  23. 23.
    G. L. Greene, L. E. Close, H. Fleming, E. R. DeSombre, E. V. Jensen, Antibodies to estrogen receptor: immunochemical similarity of estrophilin from various mammalian species. Proc. Nat. Acad. Sci. USA, 74: 3681 (1977).PubMedCrossRefGoogle Scholar
  24. 24.
    E. V. Jensen, Monoclonal antibodies as probes for estrogen receptor structure. 3rd Intl Colloq on Physiol and Chem Information Transfer in the Regulation of Reproduction and Aging. Varna Bulgaria, p. 47 (1980).Google Scholar
  25. 25.
    S. R. Glasser, F. Chytil, T. C. Spelsberg, Early effects of oestradiol-17B on the chromatin and activity of deoxyribonucleic acid-dependent ribonucleic acid polymerase (I and II) of the rat uterus. Biochem. J. 130: 947 (1972).PubMedGoogle Scholar
  26. 26.
    J. T. Knowler, R. M. S. Smellie, The oestrogen-stimulated synthesis of heterogeneous nuclear ribonucleic acid in the uterus of immature rats. Biochem. J. 131: 689 (1973).PubMedGoogle Scholar
  27. 27.
    N. M. Borthwick, R. M. S. Smellie, The effects of oestradiol 17B on ribonucleic acid polymerases of immature rabbit uterus. Biochem. J. 147: 91 (1975).PubMedGoogle Scholar
  28. 28.
    B. Ariz, J. T. Knowler, The direction of messenger ribonucleic acid sequences in heterogeneous nuclear ribonucleic acid fractions of the oestrogen-stimulated rat uterus. Biochem. J. 187–265 (1980).Google Scholar
  29. 29.
    T. J. Lindell, Inhibition of mammalian RNA polymerases in: Inhibitors of DNA and RNA Polymerases (P S Savin and R C Gallo, eds.), pp 111–137, Pergamon Press, New York (1977).Google Scholar
  30. 30.
    E. W. Benz, M. J. Getz, D. J. Wells, H. J. Moses, Nuclear RNA accumulation in cultured AKR mouse embryon cells stimulated to proliferate. Exp. Cell Res. 108: 157 (1977).PubMedCrossRefGoogle Scholar
  31. 31.
    G. S. Roth, Reduced glucocorticoid responsiveness and receptor concentration in splenic leukocytes of senescent rats. Biochem. Biophys. Acta. 399: 145 (1975).PubMedCrossRefGoogle Scholar
  32. 32.
    G. S. Roth, J. N. Livingston, Reductions in glucocorticoid inhibition of glucose oxidation and presumptive glucocorticoid receptor content in rat adipocytes during aging. Endocrinology 99: 831 (1976).PubMedCrossRefGoogle Scholar
  33. 33.
    R. C. Adelman, Age-dependent effects on enzyme induction-a biochemical expression of aging. Exp. Gerontology 6: 49 (1971).CrossRefGoogle Scholar
  34. 34.
    R. C. Adelman, G. Stein, G. S. Roth, D. Englander, Age-dependent regulation of mammalian DNA synthesis and cell proliferation in vivo. Mech. Ageing and Devel. 1: 49 (1972).CrossRefGoogle Scholar
  35. 35.
    G. S. Roth, K. Karoly, V. J. Britton, R. C. Adelman, Age dependent regulation of isoproterenol-stimulated DNA synthesis in rat salivary gland in vivo. Exp. Gerontology 9: 1 (1974).CrossRefGoogle Scholar
  36. 36.
    S. Mohla, E. R. Desombre, E. V. Jensen, Tissue-specific stimulation of RNA synthesis by transformed estradiol-receptor complex. Biochem. Biophys. Res. Comm. 46: 661 (1972).PubMedCrossRefGoogle Scholar
  37. 37.
    M. Arnaud, Y. Beziat, J. C. Duilleux, A. Hough, D. Hough, M. Mousseron-Canet, Les recepteurs de l’oestradiol dans l’uterus de genisse stimulation de la biosynthese de RNA in vitro. Biochem. Biophys. Acta. 232: 117 (1971).PubMedGoogle Scholar
  38. 38.
    W. J. King, G. L. Greene, Monoclonal antibodies localize estrogen receptor in the nuclei of target cells. Nature 307: 745 (1984).PubMedCrossRefGoogle Scholar
  39. 39.
    W. Welshons, M. E. Lieberman, J. Gorski, Nuclear localization of unoccupied estrogen receptors. Nature 307: 747 (1984).PubMedCrossRefGoogle Scholar
  40. 40.
    R. G. Cutler, Alterations with age in the information storage and flow systems of the mammalian cell. In: Genetic Effects on Aging. (D Bergsma and D. H. Harrison eds.), pp. 463–498, Alan R. Liss New York (1978).Google Scholar
  41. 41.
    S. Belisle, J. G. Lehoux, Endocrine aging in C57BL mice-II Dynamics of estrogen receptors in the hypothalamic-pituitary axis. J. Steroid Biochem. 18: 737 (1982).CrossRefGoogle Scholar
  42. 42.
    O. L. Kon, T. C. Spelsberg, Nuclear binding of estrogen-receptor complex: receptor-specific nuclear acceptor sites. Endocrinology 111: 1925 (1982).PubMedCrossRefGoogle Scholar
  43. 43.
    R. S. Chuknyisaka, M. Haji, R. H. Foote, G. S. Roth, Effect of in vivo estradiol administration on availability of rat uterine nuclear acceptor sites measured in vitro. Endocrinology 115: 836 (1984).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • George S. Roth
    • 1
  1. 1.Molecular Physiology and Genetics Section Gerontology Research Center, NIA, NIHBaltimore City HospitalsBaltimoreUSA

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