The Cellular Actions of Glucocorticoids in Relation to Human Neoplasms

  • E. Brad Thompson
Part of the Current Topics in Molecular Endocrinology book series (CTME, volume 4)


Two fundamental concepts concerning the actions of steroid hormones seem to be generally agreed upon. The first is that steroids are inducers, inducers of various specific macromolecules in appropriate target cells. To cite but a few examples, in liver and in certain cultured hepatoma cells, glucocorticoids induce increased synthesis of specific enzymes, such as tryptophan oxygenase and tyrosine aminotransferase (1–3). In immature chicks, estrogens provoke growth, as well as increased specific RNA and protein synthesis (ovalbumin) in target cells (4,5). In rat uterus overall increased growth and specific protein synthesis are induced by estrogen (4,5). Dihydrotestosterone induces several enzymes in rat kidney (6), and progesterone induces avidin in estrogen-primed chick oviduct (7). The list is long (8), and the point seems clear. Steroids are inducers of proteins, DNA, and all the various major classes of RNA. Not all effects are seen in all tissues, of course. The differentiated nature of various cell types defines whether they respond at all to steroids, and if so, to which steroids with which responses. The elements responsible for such specificity and differentiation raise the second fundamental concept in steroid hormone action.


Glucocorticoid Receptor Acute Myelogenous Leukemia Thymidine Uptake Receptor Content Competitive Binding Assay 


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  1. 1.
    Lin, E.C.C. and W.E. Knox, Biochim. Biophys. Acta 26:85, 1957.PubMedCrossRefGoogle Scholar
  2. 2.
    Kenney, F.T., J. Biol. Chem. 237:1610, 1962.PubMedGoogle Scholar
  3. 3.
    Thompson, E.B., G.M. Tonkins and J.F. Curran, Proc. Natl. Acad. Sci., U.S.A. 56:296, 1966.PubMedCrossRefGoogle Scholar
  4. 4.
    O’Malley, B.W., New Engl. J. Med. 284:370, 1971.PubMedCrossRefGoogle Scholar
  5. 5.
    Palmiter, R.D., T. Oka and R.T. Schimke, J. Biol. Chen. 246:724, 1971.Google Scholar
  6. 6.
    Paigen, K., R.T. Swank, S. Tornino and R.E. Ganschow, J. Cell Physiol. 85:379, 1975.PubMedCrossRefGoogle Scholar
  7. 7.
    Korenman, S.G. and B.W. O’Malley, Endocrinology 83:11, 1968.PubMedCrossRefGoogle Scholar
  8. 8.
    Pitot, H.C. and M.B. Yatvin, Physiol. Rev. 53:228, 1973.PubMedGoogle Scholar
  9. 9.
    Jensen, E.V., S. Mohla, T.A. Gorell and E.R. DeSombre, Vitamins and Hormones 32:89, 1974.PubMedCrossRefGoogle Scholar
  10. 10.
    King, R.J.B. and W.I.P. Mainwaring, Steroid-Cell Interactions, Univ. Park Press, Baltimore, 1974, p. 430.Google Scholar
  11. 11.
    DeSombre, E.R., J.P. Chaband, G.A. Puca and E.V. Jensen, J. Steroid Biochera. 3:445, 1972.CrossRefGoogle Scholar
  12. 12.
    Jensen, E.V., S. Mohla, T. Gorell, S. Tanaka and E.R. De Sombre, J. Steroid Biochem. 3:445, 1972.PubMedCrossRefGoogle Scholar
  13. 13.
    Failla, D., G.M. Tomkins and D.V. Santi, Proc. Natl. Acad. Sci., U.S.A. 72:3849, 1975.PubMedCrossRefGoogle Scholar
  14. 14.
    Schrader, W.T. and B.W. O’Malley, J. Biol. Chem. 247:51, 1972.PubMedGoogle Scholar
  15. 15.
    Rousseau, G.G., J.D. Baxter and G.M. Tomkins, J. Mol. Biol. 62:99, 1972.CrossRefGoogle Scholar
  16. 16.
    Pratt, W.B., J.L. Kaine and D.V. Pratt, J. Biol. Chem. 250: 4584, 1975.PubMedGoogle Scholar
  17. 17.
    Mosher, K.M., D.A. Young and A. Munck, J. Biol. Chem. 246: 654, 1971.PubMedGoogle Scholar
  18. 18.
    Chan, L., A.R. Means and B.W. O’Malley, Proc. Natl. Acad. Sci., U.S.A. 70:1870, 1973.PubMedCrossRefGoogle Scholar
  19. 19.
    Schutz, G., G. Killewich, G. Chen and P. Feigelson, Proc. Natl. Acad. Sci., U.S.A. 72:1017, 1975.PubMedCrossRefGoogle Scholar
  20. 20.
    Schwartz, R.J., Nature New Biol. 237:121, 1972.PubMedGoogle Scholar
  21. 21.
    Makman, M.H., S. Nakagawa and A. White, Rec. Progr. Horm. Res. 23:195, 1967.PubMedGoogle Scholar
  22. 22.
    Earle, W.R., J. Nat. Cancer Inst. 4:165, 1943.Google Scholar
  23. 23.
    Pratt, W.B. and L. Aronow, J. Biol. Chem. 241:5244, 1966.PubMedGoogle Scholar
  24. 24.
    Henderson, T.C., R.E. Fischel and J.N. Loeb, Endocrinology 88:1471, 1971.PubMedCrossRefGoogle Scholar
  25. 25.
    Loeb, J.N, C. Borek and L.L. Yeung, Proc. Natl. Acad. Sci., U.S.A. 70:3852, 1973.PubMedCrossRefGoogle Scholar
  26. 26.
    Rosenau, W., J.D. Baxter, G.G. Rousseau and G.M. Tomkins, Nature New Biol. 237:20, 1972.PubMedCrossRefGoogle Scholar
  27. 27.
    Kirkpatrick, A.F., R.J. Milholland and F. Rosen, Nature New Biol. 232:216, 1971.PubMedGoogle Scholar
  28. 28.
    Munck, A.C. Wira, D.A. Young, K.M. Mosher, C. Hallahan and P.A. Bell, J. Steroid Biochem. 3:567, 1972.PubMedCrossRefGoogle Scholar
  29. 29.
    Hackney, J.P., S.R. Gross, L. Aronow and W.B. Pratt, Mol. Pharmacol. 6:500, 1970.PubMedGoogle Scholar
  30. 30.
    Baxter, J.D., A.W. Harris, G.M. Tomkins and M. Cohn, Science 171:189, 1971.PubMedCrossRefGoogle Scholar
  31. 31.
    Aronow, L. and J.D. Gabourel, Proc. Soc. Exp. Biol. Med. 111: 348, 1962.Google Scholar
  32. 32.
    Kirkpatrick, A.F., R.J. Milholland and F. Rosen, Nature New Biol. 232:216, 1971.PubMedGoogle Scholar
  33. 33.
    Kaiser, N., R.J. Milholland and F. Rosen, Cancer Res. 34: 621, 1974.PubMedGoogle Scholar
  34. 34.
    Sibley, C.H. and G.M. Tomkins, Cell 2:213, 1974.PubMedCrossRefGoogle Scholar
  35. 34a.
    Sibley, C.H. and G.M. Tomkins, Cell 2:221, 1974.PubMedCrossRefGoogle Scholar
  36. 35.
    Lippman, M.E. and E.B. Thompson, J. Biol. Chem. 249:2483, 1974.PubMedGoogle Scholar
  37. 36.
    Pratt, W.B. and D.N. Ishii, Biochem. 11:1401, 1972.CrossRefGoogle Scholar
  38. 37.
    Mosher, K.M., D.A. Young and A. Munck, J. Biol. Chem. 246: 654, 1971.PubMedGoogle Scholar
  39. 38.
    Makman, M.H, B. Dvorkin and A White, Proc. Natl. Acad, Sci., U.S.A. 68:1269, 1971.CrossRefGoogle Scholar
  40. 39.
    Makraan, M.H., B. Dvorkin and A. White, J. Biol. Chem. 245: 2556, 1970.Google Scholar
  41. 40.
    White, A. and M.H. Makman, Adv. Enz. Res. 5:317, 1967.CrossRefGoogle Scholar
  42. 41.
    Jensen, E.V., G.E. Block, S. Smith, K. Kyser and E.R. DeSombre, Nat. Cancer Inst. Monograph 34 :55, 1971.Google Scholar
  43. 42.
    McGuire, W.L., P.P. Carbone and E.P. Vollmer (eds), Estrogen Receptors in Human Breast Cancer, Raven Press, New York, 1975.Google Scholar
  44. 43.
    Ranney, H. and A. Gellhorn, Amer. J. Med. 22:405, 1957.PubMedCrossRefGoogle Scholar
  45. 44.
    Granville, N., F. Rubio Jr., A. Unugur, E. Schulman and W. Dameshek, New Engl. J. Med. 259:207, 1958.PubMedCrossRefGoogle Scholar
  46. 45.
    Shanbrom, E. and S. Miller, New Engl. J. Med. 266:1354, 1962.PubMedCrossRefGoogle Scholar
  47. 46.
    Henderson, E.S., Semin. Hematol. 6:271, 1969.PubMedGoogle Scholar
  48. 47.
    Schrek, R., J. Natl. Cancer Inst. 33:837, 1964.PubMedGoogle Scholar
  49. 48.
    Cline, M.J. and E. Rosenbaum, Cancer Res. 28:2516, 1968.PubMedGoogle Scholar
  50. 49.
    Cline, M.J., Blood 30:176, 1967.PubMedGoogle Scholar
  51. 50.
    Werthamer, S. and L. Amaral, Blood 37:463, 1971.PubMedGoogle Scholar
  52. 51.
    Lippman, M.E., R.H. Halterman, B.G. Leventhal, S. Perry and E.B. Thompson, J. Clin. Invest. 52:1715, 1973.PubMedCrossRefGoogle Scholar
  53. 52.
    Lippman, M.E., R. Halterman, S. Perry, B. Leventhal and E.B. Thompson, Nature New Biol. 242:15 7, 1973.Google Scholar
  54. 53.
    Scatchard, G., Ann. N.Y. Acad. Sci. 51:660, 1949.CrossRefGoogle Scholar
  55. 54.
    Munck, A. and C. Wira, In: Raspe, G. (ed.), Advances in the Biosciences 7, Schering Workshop on Steroid Hormone Receptors, Pergamon Press, New York, 1971, p. 301.Google Scholar
  56. 55.
    Claman, H.N., J.W. Moorhead and W.H. Benner, J. Lab. Clin. Med. 78:499, 1971.PubMedGoogle Scholar
  57. 56.
    Roath, S., M. Israels, J. Wilkinson, Quart. J. Med. 33:257, 1964.Google Scholar
  58. 57.
    Lippman, M.E., S. Perry and E.B. Thompson, Amer. J. Med. 59: 224, 1975.PubMedCrossRefGoogle Scholar
  59. 58.
    Munck, A., Perspect. Biol. Med. 14:265, 1971.PubMedGoogle Scholar
  60. 59.
    Gailani, S., J. Minowada, P. Silvernail, A. Nussbaum, N. Kaiser, F. Rosen and K. Shimaoka, Cancer Res. 33:2653, 1973.PubMedGoogle Scholar
  61. 60.
    Yates, F.E., D.J. Marsh and J.W. Maran, In: Mountcastle, (ed.), Medical Physiology, Vol. 2, The C.V. Mosby Co., St. Louis, 1974, p. 1696.Google Scholar
  62. 61.
    Baumann, G., G. Rappaport, T. Lemarchand-Berand and J. Felber, J. Clin. Endocrinol. Metab. 40:462, 1975.PubMedCrossRefGoogle Scholar
  63. 62.
    Kaiser, N., R.J. Milholland and F. Rosen, Cancer Res. 34: 621, 1974.PubMedGoogle Scholar
  64. 63.
    Yamamoto, K.R., M.R. Stampfer and G.H. Tomkins, Proc. Natl. Acad. Sci., U.S.A. 71:3901, 1974.PubMedCrossRefGoogle Scholar
  65. 64.
    Lippman, M.E., S. Perry and E.B. Thompson, Cancer Res. 34: 1572, 1974.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • E. Brad Thompson
    • 1
  1. 1.Laboratory of Biochemistry, National Cancer InstituteNational Institutes of HealthBethesdaMaryland

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