Regulation and Function of Estrogen and Progesterone Receptor Systems

  • Wendell W. Leavitt
  • Tong J. Chen
  • Rawden W. Evans
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 117)


We have developed and validated assay methods which are appropriate for studying the subcellular distribution of estrogen receptor (Re) and progesterone receptor (Rp) in hamster uterus during the estrous cycle and pregnancy. Cytosol receptors were monitored by conventional procedures, and nuclear receptors were extracted from nuclei at 2 C using 0.5 M KC1 in buffer containing glycerol and measured by ligand exchange during incubation with [3H] progesterone (P) at 2 C for 24 h or [3H] estradiol-17ß (E2) at 30 C for 1 h. The nuclear exchange assay described herein measures total receptor and also permits estimation of unlabeled steroid in the nuclear KC1 extract. Nuclear Rp translocation was shown to be target-tissue specific, hormone specific, and dependent on P dosage under in vivo conditions. The duration of nuclear Rp retention was about 6 h following exogenous P treatment. During the estrous cycle, Re and Rp levels in uterine cytosol and nuclei varied in response to the changing pattern of E2 and P secretion. Our results document a positive relationship between serum E2, nuclear Re and cytosol Rp levels during the follicular phase of the cycle. Nuclear Rp remained low on cycle days 1–3, and increased abruptly on day 4 coincident with preovulatory P secretion and cytosol Rp depletion. Nuclear Rp translocation during the preovulatory period on cycle day 4 was associated with a marked decline in nuclear Re, and the latter was demonstrated to be a rapid (2–4 h) response to P action rather than serum E2 withdrawal. The negative effect of P on nuclear Re levels may represent a fundamental mechanism for P antagonism of E action. Cytosol and nuclear Rp levels in deciduomal and myometrial tissue were responsive to experimental alteration of serum P, indicating that nuclear Rp is maintained by a continuous process of P-induced Rp translocation. Of interest was the finding in pregnant animals that Re levels declined dramatically in deciduoma as compared to myometrium. The loss of cytosol and nuclear Re from deciduomal cells cannot be attributed to changes in serum E2 or P. Thus, the intracellular regulation of Re numbers may change during differentiation of certain target cells such as those found in the deciduoma.


Nuclear Extract Estrous Cycle Follicular Phase Nuclear Fraction Intact Nucleus 
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  1. 1.
    Chan, L., and B. W. O’Malley (1976) N Engl J Med 294: 1322 1328.Google Scholar
  2. 2.
    Schrader, W. T., and B. W. O’Malley (1978). In O’Malley, B.W., and L. Birnbaumer. “Receptors and Hormone Action” Vol 2, Academic Press, New York, pp 189–224.Google Scholar
  3. 3.
    Leavitt, W. W., T. J. Chen, Y. S. Do, B. D. Carlton, and T. C. Allen (1978). Ibid. pp 157–188.Google Scholar
  4. 4.
    Sar, M., and W. E. Stumpf (1974) Endocrinology 94: 1116–1125.PubMedCrossRefGoogle Scholar
  5. 5.
    Warembourg, M., and E. Milgrom (1977) Endocrinology 100: 175–181.PubMedCrossRefGoogle Scholar
  6. 6.
    Feil, P. D., and C. W. Bardin (1975) Endocrinology 97: 1398–1407.PubMedCrossRefGoogle Scholar
  7. 7.
    Faber, L. E., J. Saffran, T. J. Chen, and W. W. Leavitt (1976). In Menon, K. M. J., and J. R. Reel. “Steroid Hormone Action and Cancer,” Plenum Pub. Corp., New York, pp 68–84.CrossRefGoogle Scholar
  8. 8.
    Saffran, J., B. K. Loeser, S. A. Bohnett, and L. E. Faber (1976) J Biol Chem 251: 5607–5613.PubMedGoogle Scholar
  9. 9.
    Milgrom, E., L. Thi, M. Atger, and E.-E. Baulieu (1973) J Biol Chem 248: 6366–6374.PubMedGoogle Scholar
  10. 10.
    Leavitt, W. W., D. 0. Toft, C. A. Strott, and B. W. O’Malley (1974) Endocrinology 94: 1041–1053.PubMedCrossRefGoogle Scholar
  11. 11.
    Freifeld, M. L., P. D. Feil, and C. W. Bardin (1974) Steroids 23: 93–103.PubMedCrossRefGoogle Scholar
  12. 12.
    Clark, J. H., E. J. Peck, Jr., W. T. Schrader, and B. W. O’Malley (1976). Methods in Cancer Research 12: 367–417.Google Scholar
  13. 13.
    Anderson, J., J. H. Clark, and E. J. Peck, Jr. (1972) Biochem J 126: 561–567.PubMedGoogle Scholar
  14. 14.
    Anderson, J., E. J. Peck, Jr., and J. H. Clark (1975) Endocrinology 96: 160–167.PubMedCrossRefGoogle Scholar
  15. 15.
    Zava, D. T., N. Y. Harrington, and W. L. McGuire (1976) Biochemistry 15: 4292–4297.PubMedCrossRefGoogle Scholar
  16. 16.
    Clark, J. H., and E. J. Peck, Jr. (1976) Nature 260: 635–636.PubMedCrossRefGoogle Scholar
  17. 17.
    Juliano, J. V., and M. G. Stancel (1976) Biochemistry 15: 916–920.PubMedCrossRefGoogle Scholar
  18. 18.
    Traish, A. M., R. E. Müller, and H. H. Wotiz (1977). J Biol Chem 252: 6823–6830.PubMedGoogle Scholar
  19. 19.
    Müller, R. E., A. M. Traish, and H. H. Wotiz (1977) J Biol Chem 252: 8206–8211.PubMedGoogle Scholar
  20. 20.
    Do, Y.S., and W. W. Leavitt (1978) Endocrinology 102: 443–451.PubMedCrossRefGoogle Scholar
  21. 21.
    Chen, T. J., and W. W. Leavitt (1979) Endocrinology (in press).Google Scholar
  22. 22.
    Moudgil, V. K., and D. 0. Toft (1975) Proc Natl Acad Sci USA 72: 901–905.PubMedCrossRefGoogle Scholar
  23. 23.
    Kupfer, D., and W. H. Bulger (1976) Fed Proc 35: 2603–2608.PubMedGoogle Scholar
  24. 24.
    Sedmak, J. J., and S. E. Grossberg (1977). Annal Biochem 79: 544–552.CrossRefGoogle Scholar
  25. 25.
    Astwood, E. B. (1939) J Endocrinology 1: 49–55.CrossRefGoogle Scholar
  26. 26.
    Harper, M. J. K. (1970) Anat Rec 167: 225–230.PubMedCrossRefGoogle Scholar
  27. 27.
    Glasser, S. R., and J. H. Clark ( 1975. In “The Developmental Biology of Reproduction,” C. L. Markert, and J. Papconstantinou, Academic Press, New York pp 311–345.Google Scholar
  28. 28.
    Cohen, S. S. (1971) “Introduction to the Polyamines,” Prentice Hall, Inc., Englewood Cliffs, New Jersey.Google Scholar
  29. 29.
    Raina, A., and J. J. JHnne (1975) Med Biol 53: 121–147.PubMedGoogle Scholar
  30. 30.
    Barkai, U., and P. F. Kraicer (1978) Int J Fertil 23: 106–111.PubMedGoogle Scholar
  31. 31.
    West, N. B., R. L. Norman, B. A. Sandow, and R. M. Brenner (1978) Endocrinology 103: 1732–1741.PubMedCrossRefGoogle Scholar
  32. 32.
    Brenner, R. M., and N. B. West (1975) Ann Rev Physiol 37: 273402.Google Scholar
  33. 33.
    Bhakoo, H. S., and B. S. Katzenellenbogen (1977) Mol Cell Endocrinology 8: 121–134.CrossRefGoogle Scholar
  34. 34.
    Hsueh, A. J. W., E. J. Peck, Jr., and J. H. Clark (1976) Endocrinology 98: 438–444.PubMedCrossRefGoogle Scholar
  35. 35.
    Clark, J. H., A. J. W. Hsueh, and E. J. Peck, Jr. (1977) Ann N Y Acad Sci 286: 161–176.PubMedCrossRefGoogle Scholar
  36. 36.
    Walters, M. R., and J. H. Clark (1978) Endocrinology 103: 601–609.PubMedCrossRefGoogle Scholar
  37. 37.
    Walters, M. R., and J. H. Clark (1978) Endocrinology 103: 1952–1955.PubMedCrossRefGoogle Scholar
  38. 38.
    VuHai, M. T., F. Logeat, and E. Milgrom (1978). J Endocrinol 76: 43–48.CrossRefGoogle Scholar
  39. 39.
    Butcher, R. L., W. E. Collins, and N W. Fugo (1974) Endocrinology 94: 1704–1708.PubMedCrossRefGoogle Scholar
  40. 40.
    Bosley, C. G., and W. W. Leavitt (1972) Am J Physiology 222: 129–133.Google Scholar
  41. 41.
    Kimmel, G. L., B. C. Moulton, and W. W. Leavitt (1973) J Endocrinol 56: 335–336.PubMedCrossRefGoogle Scholar
  42. 42.
    Talley, D. J., J. A. Tobert, E. G. Armstrong, Jr., and C. A. Villee (1977) Endocrinology 101: 1538–1544.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1979

Authors and Affiliations

  • Wendell W. Leavitt
    • 1
  • Tong J. Chen
    • 1
  • Rawden W. Evans
    • 1
  1. 1.Worcester Foundation for Experimental BiologyShrewsburyUSA

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