Klinische Wochenschrift

, Volume 63, Issue 15, pp 689–698 | Cite as

Glucocorticoid receptors in human leukemias and related diseases

  • E. B. Thompson
  • J. R. Smith
  • S. Bourgeois
  • J. M. Harmon
Übersichten

Summary

The evidence to date is compelling that steroid initiated cell lysis involves participation of the glucocorticoid receptor. Not only do the concentrations and specificity of hormones for cell lysis and receptor occupancy correspond, but also steroid resistant cells selected with or without prior mutagenesis often have altered receptors. The glucocorticoid receptor protein from humans and other species is a ∼ 95,000 d, thiol group-containing monomer, prone to aggregation when “unactivated.” After having bound steroid and been “activated,” the monomeric steroid-receptor complex is altered in charge and shape so that its binding to chromatin and DNA is greatly enhanced. Simple measurement of numbers of receptor sites in cells from patients with various blood dyscrasias has given, in some diseases, good correlations between high numbers of receptor sites and good therapeutic response. These correlations are strongest for childhood acute lymphoblastic leukemia (ALL) and for non Hodgkins' lymphoma. In other diseases, notably acute myelogenous leukemia, such correlations have not been found.

The CEM human ALL line has been used in vitro to study mechanisms of glucocorticoid action and resistance. The requirement for “activated” steroid-receptor complex for cell lysis is shown in these cells by the spontaneous occurrence of steroid resistant, activation-labile receptor mutants. A second category of resistant cells with normal receptors has been defined. Treatment of these “lysis defective” resistant cells with compounds which result in DNA demethylation can render them steroid sensitive. Since DNA demethylation can allow formerly silent genes to become transcribed, it is possible that one or more genes specific for lysis has been “opened” in such cells. Alternatively, DNA demethylation may produce a general biochemical effect on the cell which renders it susceptible to lysis. Mutagenized CEM cells selected for steroid resistance give rise to a third class of mutants, which are deficient in receptor quantity. Each of these classes of steroid resistant cells contains information pertinent to understanding the use of glucocorticoids and the role of glucocorticoid receptors in human leukopathic disease.

Key words

Glucocorticoids Receptors Leukemia Tissue Culture Resistance 

Abbreviations

ALL

acute lymphoblastic leukemia

AML

acute myelogenous leukemia

CLL

chronic lymphoblastic leukemia

Da

Dalton

RP/HPLC

reverse phase/high performance liquid chromatography

SDS

sodium dodecyl sulfate

SRBC

sheep red blood cells

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Wrange O, Okret S, Radojcic M, Carlstedt-Duke J, Gustafsson J-A (1983) Characterization of the purified glucocorticoid receptor from rat liver cytosol. In: Eriksson H, Gustaffson J-A (eds) Steroid Hormone Receptors: Structure and Function. Elsevier, Amsterdam, pp 73–90Google Scholar
  2. 2.
    Wrange O, Gustafsson J-A (1978) Separation of the hormone- and DNA-binding sites of the hepatic glucocorticoid receptor by means of proteolysis. J Biol Chem 253:856–865Google Scholar
  3. 3.
    Okret S, Carlstedt-Duke J, Wrange O, Carlstrom K, Gustafsson J-A (1981) Characterization of an antiserum against the glucocorticoid receptor. Biochim Biophys Acta 677:205–219Google Scholar
  4. 4.
    Carlstedt-Duke J, Okret S, Wrange O, Gustafsson J-A (1982) Immunochemical analysis of the glucocorticoid receptor: Identification of a third domain separated from the steroid-binding and DNA-binding domains. Proc Natl Acad Sci USA 79:4260–4264Google Scholar
  5. 5.
    Wrange O, Carlstedt-Duke J, Gustafsson J-A (1979) Purification of the glucocorticoid receptor from rat liver cytosol. J Biol Chem 254:9284–9290Google Scholar
  6. 6.
    Govindan MV, Sekeris CE (1978) Purification of two dexamethasone-binding proteins from rat-liver cytosol. Eur J Biochem 89:95–104Google Scholar
  7. 7.
    Govindan MV, Manz B (1980) Three-step purification of glucocorticoid receptors from rat liver. Eur J Biochem 108:47–53Google Scholar
  8. 8.
    Eisen H, Schleenbaker RE, Simons SS (1981) Affinity labeling of the rat liver glucocorticoid receptor with dexamethasone 21-mesylate. J Biol Chem 256:12920–12925Google Scholar
  9. 9.
    Simons SS, Thompson EB (1981) Dexamethasone 21-mesylate: An affinity label of glucocorticoid receptors from rat hepatoma tissue culture cells. Proc Natl Acad Sci USA 78:3541–3545Google Scholar
  10. 10.
    Thompson EB, Zawydiwski R, Brower ST, Eisen HJ, Simons SS, Schmidt TJ, Schlechte JA, Moore DE, Norman MR, Harmon JM (1983) Properties and function of human glucocorticoid receptors in steroid-sensitive and -resistant leukemic cells. In: Eriksson H, Gustafsson J-A (eds) Steroid Hormone Receptors: Structure and Function. Elsevier, Amsterdam, 1983, pp 171–192Google Scholar
  11. 11.
    Harmon JM, Eisen HJ, Brower ST, Simons SS Jr, Langley CL, Thompson EB (1985) Identification of human leukemic glucocorticoid receptors using affinity labeling and anti-human glucocorticoid receptor antibodies. Cancer Res (In press)Google Scholar
  12. 12.
    Sherman MR, Tuazon FB, Stevens Y-W, Niu E-M (1983) Oligomeric steroid receptor forms and the products of their dissociation and proteolysis. In: Eriksson H, Gustafsson J-A (eds) Steroid Hormone Receptors: Structure and Function, Elsevier, Amsterdam, pp 3–23Google Scholar
  13. 13.
    Sherman MR, Stevens J (1984) Structure of mammalian steroid receptors: Evolving concepts and methodological developments. Ann Rev Physiol 46:83–105Google Scholar
  14. 14.
    Sherman MR, Moran MC, Tuazon FB, Stevens Y-W (1983) Structure, dissociation, and proteolysis of mammalian steriod receptors. J Biol Chem 258:10366–10377Google Scholar
  15. 15.
    Grandics P, Miller A, Schmidt TJ, Mittman D, Litwack G (1984) Purification of the unactivated glucocorticoid receptor and its subsequent in vitro activation. J Biol Chem 259:3173–3180Google Scholar
  16. 16.
    Zawydiwski R, Harmon JM, Thompson EB (1983) Glucocorticoid-resistant human acute lymphoblastic leukemia cell line with functional receptor. Cancer Res 43:3865–3873Google Scholar
  17. 17.
    Niu E-M, Neal RM, Pierce VK, Sherman MR (1981) Structure similarity of molybate-stabilized steroid receptor in human breast tumors, uteri and leukocytes. J Steroid Biochem 15:1–10Google Scholar
  18. 18.
    Holbrook NJ, Bodwell JE, Jeffries M, Munck A (1983) Characterization of nonactivated and activated glucocorticoid-receptor complexes from intact rat thymus cells. J Biol Chem 258:6477–6485Google Scholar
  19. 19.
    Vedeckis WV (1981) Activation and chromatographic properties of the A&T-20 mouse pituitary tumor cell line glucocorticoid receptor. Biochemistry 20:7237–7245Google Scholar
  20. 20.
    Currie RA, Cidlowski JA (1982) Physicochemical properties of the cytoplasmic glucocorticoid receptor complex in HeLa S3 cells. J Steroid Biochem 16:419–428Google Scholar
  21. 21.
    Westphal HM, Beato M (1980) The activated glucocorticoid receptor of rat liver. Purification and physical characterization. Eur J Biochem 106:395–403Google Scholar
  22. 22.
    Sherman MR, Stevens Y-W, Tuazon FB (1984) Multiple forms and fragments of cytosolic glucocorticoid receptors from human leukemic cells and normal lymphocytes. Cancer Res 44:3783–3796Google Scholar
  23. 23.
    Gametchu B, Harrison RW (1984) Characterization of a monoclonal antibody to the rat liver glucocorticoid receptor. Endocrinology 114:274–279Google Scholar
  24. 24.
    Gustafsson JA, Okret S, Wikstrom A-C, Andersson B, Radojcic M, Wrange O, Sachs W, Doupe AJ, Patterson PH, Cordell B, Fuxe K (1983) On the use of poly- and monoclonal antibodies in studies on the structure and function of the glucocorticoid receptor. In: Eriksson H, Gustafsson J-A (eds) Steroid Hormone Receptors: Structure and Function, Elsevier, Amsterdam, pp 355–386Google Scholar
  25. 25.
    Barnett CA, Schmidt TJ, Litwack G (1980) The effects of calf intestinal alkaline phosphatase, phosphatase inhibitors and phosphorylated compounds on the rate of activation of glucocorticoid-receptor complexes. Biochemistry 19:5446–5455Google Scholar
  26. 26.
    Housley PR, Grippo JF, Dahmer MK, Pratt WB (1984) Inactivation, activation and stabilization of glucocorticoid receptors. In: Litwack G (ed) Biochemical Actions of Hormones, Vol XI, Academic Press, New York, pp 347–376Google Scholar
  27. 27.
    Cidlowski JA (1980) Pyridoxal phosphate induced alterations in glucocorticoid receptor metabolism by proteases. Biochem 19:6162–6170Google Scholar
  28. 28.
    Cake MH, Goidl JA, Parchman LG, Litwack G (1976) Involvement of a low molecular weight component(s) in the mechanism of action of the glucocorticoid receptor. Biochem Biophys Res Commun 71:45–52Google Scholar
  29. 29.
    Cake MH, Disorbo DM, Litwack G (1978) Effect of pyridoxal on the DNA binding site of the activated hepatic glucocorticoid receptor. J Biol Chem 253:4886–4891Google Scholar
  30. 30.
    Isohashi F, Horiuchi M, Okamoto K, Sakamoto Y (1984) Separation and characterization of receptor-translocation inhibitors from AH130 tumor cells. J Steroid Biochem 20:1117–1122Google Scholar
  31. 31.
    Sato B, Noma K, Nishizawa Y, Nakoo K, Matsumoto K, Yamamura Y (1980) Mechanism of activation of steroid receptors: Involvement of low molecular weight inhibitor in activation of androgen, glucocorticoid, and estrogen receptor systems. Endocrinol 106:1142–1148Google Scholar
  32. 32.
    Sakaue Y, Thompson EB (1977) Characterization of two forms of glucocorticoid hormone-receptor complex separated by DEAE-cellulose column chromatography. Biochem Biophys Res Commun 77:533–541Google Scholar
  33. 33.
    Parchman LG, Litwack G (1977) Resolution of activated and unactivated forms of the glucocorticoid receptor from rat liver. Arch Biochem Biophys 183:374–382Google Scholar
  34. 34.
    Munck A, Foley R (1979) Activation of steroid hormone-receptor complexes in intact target cells in physiological conditions. Nature 278:752–754Google Scholar
  35. 35.
    Munck A, Foley R (1980) Activated and non-activated glucocorticoid receptor complexes in rat thymus cells: kinetics of formation and relation to steroid structure. J Steroid Biochem 12:225–230Google Scholar
  36. 36.
    Stevens J, Stevens Y (1979) Physicochemical differences between glucocorticoid-binding components from the corticoid-sensitive and -resistant strains of mouse lymphoma. Cancer Res 39:4011–4021Google Scholar
  37. 37.
    Stevens J, Stevens Y (1981) Influence of limited proteolysis on the physicochemical and DNA-binding properties of glucocorticoid receptors from corticoid-sensitive and-resistant mouse lymphoma P1798. Cancer Res 41:125–133Google Scholar
  38. 38.
    Norman MR, Thompson EB (1977) Characterization of a glucocorticoid-sensitive human lymphoid cell line. Cancer Res 37:3785–3791Google Scholar
  39. 39.
    Thompson EB, Lippman ME (1974) Mechanism of action of glucocorticoids. Metabolism 23:159–202Google Scholar
  40. 40.
    Schmidt TJ, Thompson EB (1978) Glucocorticoid receptor function in leukemic cells. In: Sharma RK, Criss WE (eds) Endocrine Control in Neoplasia. Raven Press, New York, pp 263–290Google Scholar
  41. 41.
    Bourgeois S, Newby RF, Huet M (1978) Glucocorticoid resistance in murine lymphoma and thymona lines. Cancer Res 38:4279–4284Google Scholar
  42. 42.
    Sibley CH, Yamamoto KR (1979) Mouse lymphoma cells: Mechanism of resistance of glucocorticoids. In: Baxter JD, Rousseau GG (eds) Glucocorticoid Hormone Action. Springer, Berlin, pp 357–376Google Scholar
  43. 43.
    Harmon JM, Thompson EB (1981) Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM C7. Mol Cell Biol 1:512–521Google Scholar
  44. 44.
    Lippman ME, Halterman RH, Leuenthal BC, Perry S, Thompson EB (1973) Glucocorticoid-binding proteins in human acute lymphoblastic leukemic blast clells. J Clin Invest 52:1715–1725Google Scholar
  45. 45.
    Stevens J, Stevens Y-W (1984) Glucocorticoid receptors in human leukemia and lymphoma: Quantitation and clinical significance. In: Hollander VP (ed) Hormone Responsive Tumors (in press)Google Scholar
  46. 46.
    Kaplan J, Ravindranath Y, Peterson WD Jr (1977) T and B lymphocyte antigen-positive null cell leukemias. Blood 49:371–378Google Scholar
  47. 47.
    Greaves M, Janossy G (1978) Patterns of gene expression and the cellular origins of human leukaemias. Biochim Biophys Acta 516:193–230Google Scholar
  48. 48.
    Greaves MF, Delia D, Katz F, Scheider C, Sutherland R, Newman R (1983) Biological diversity of acute lymphoblastic leukemia. In: Murphy S, Gilbert JR (eds) Leukemia Research: Advances Biology and Treatment, Elsevier Biomedical, New York, pp 97–112Google Scholar
  49. 49.
    Sallan SE, Weinstein HJ (1981) Childhood Leukemia. In: Nathan DG, Oski FA (eds) Hematology of Infancy and Childhood, Vol II. W.B. Saunders, PhiladelphiaGoogle Scholar
  50. 50.
    Foon KA, Schroff RW, Gale RP (1982) Surface markers on leukemia and lymphoma cells: Recent advances. Blood 60:1–19Google Scholar
  51. 51.
    Rousseau GG, Baxter JD (1979) Tissue and species specificity. In: Baxter JD, Rousseau GG (eds) Glucocorticoid Hormone Action. Springer, New York, pp 68–69Google Scholar
  52. 52.
    Konior GS, Lippman ME, Johnson GE, Leventhel BG (1977) Glucocorticoid receptors in subpopulations of childhood acute lymphocytic leukemia. Cancer Res 37:2688–2695Google Scholar
  53. 53.
    Costlow ME, Pui C, Dahl GV (1982) Glucocorticoid receptors in childhood acute lymphoblastic leukemia. Cancer Res 42:4801–4806Google Scholar
  54. 54.
    Mastrangelo R, Malandrino, Riccardi R, Longo P, Ranelletti FO, Jacobelli S (1980) Clinical implications of glucocorticoid receptor studies in childhood acute lymphoblastic leukemia. Blood 56:1036–1040Google Scholar
  55. 55.
    Ho AD, Hunstein W, Schmid W (1981) Glucocorticoid receptors and sensitivity in leukemias. Blut 42:183–190Google Scholar
  56. 56.
    Lippman ME, Yarbro GK, Leventhal BG (1978) Clinical implications of glucocorticoid receptors in human leukemia. Cancer Res 38:4251–4256Google Scholar
  57. 57.
    McGuire WL (1980) An update on estrogen and progesterone receptors in prognosis for primary and advanced breast cancer. In: Iacobelli S, King RJB, Lindner HR, Lippman ME (eds) Hormones and Cancer, Vol 14, Raven Press, New York, pp 337–343Google Scholar
  58. 58.
    Bloomfield CD, Peterson BA, Zaleskas J, Frizzera G, Smith KA, Hilebrandt L, Gajl-Peczalska K, Munck A (1980) In-vitro glucocorticoid studies for predicting response to glucocorticoid therapy in adults with malignant lymphoma. The Lancet 1:952–956Google Scholar
  59. 59.
    Terenius B, Simonsson B, Nilsson K (1978) Glucocorticoid receptors in chronic lymphocytic leukaemia. In: Bell PA, Brothwick NM (eds) Glucocorticoid Action and Leukaemia, 7th Tenovus Workshop, Alpha Omega, Cardiff, pp 155–159Google Scholar
  60. 60.
    Schmidt TJ, Thompson EB (1979) Glucocorticoid receptors and glutamine synthetase in leukemic Sezary cells. Cancer Res 39:376–382Google Scholar
  61. 61.
    Lippman ME, Yarbro GSK, Leventhal BG (1978) Glucocorticoid receptors in normal and leukaemic human leucocytes. In: Bell PA, Borthwick NM (eds) Glucocorticoid Action and Leukaemia, 7th Tenovus Workshop, Alpha Omega, Cardiff, pp 175–190Google Scholar
  62. 62.
    Crabtree G, Smith K, Munck A (1978) Glucocorticoid receptors and sensitivity of isolated human leukemia and lymphoma cells. Cancer Res 38:4268–4272Google Scholar
  63. 63.
    Iacobelli S, Ranelletti F, Longo FO, Riccardi P, Mastrangelo R (1978) Discrepancies between in vivo and in vitro effects of glucocorticoids in myelomonocytic leukemic cells with steroid receptors. Cancer Res 38:4257–4262Google Scholar
  64. 64.
    Lippman ME, Perry S, Thompson EB (1975) Glucocorticoid binding proteins in myeloblasts of acute myelogenous leukemia. Am J Med 59:224–227Google Scholar
  65. 65.
    Holbrook NJ, Bloomfield CD, Munck A (1984) Stabilization of labile glucocorticoid-receptor complexes from acute nonlymphocytic leukemia cells by a factor from chronic lymphocytic leukemia cells. Cancer Res 44:407–414Google Scholar
  66. 66.
    Baxter JD, Harris AW, Tomkins GM, Cohn M (1971) Glucocorticoid receptors in lymphoma cells in culture: relationship to killing activity. Science 171:189–191Google Scholar
  67. 67.
    Sibley CH, Tomkins GM (1974) Isolation of lymphoma cell variants resistant to killing by glucocorticoids. Cell 2:213–220Google Scholar
  68. 68.
    Sibley CH, Tomkins GM (1974) Isolation of lymphoma cell variants resistant to killing by glucocorticoids. Cell 2:221–227Google Scholar
  69. 69.
    Foley GE, Lazarus H, Farber S, Uzman BF, Boone BA, McCarthy RE (1965) Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia. Cancer 18:522–529Google Scholar
  70. 70.
    Thompson EB, Norman MR, Lippman ME (1977) Steroid hormone actions in tissue culture cells and cell hybrids-their relation to human malignancies. Rec Prog Horm Res 33:571–615Google Scholar
  71. 71.
    Norman MR, Harmon JM, Thompson EB (1978) Use of a human lymphoid cell line to evaluate interactions between prednisolone and other chemotherapeutic agents. Cancer Res 38:4273–4278Google Scholar
  72. 72.
    Harmon JM, Norman MR, Thompson EB (1979) Human leukemic cells in culture-A model system for the study of glucocorticoid-induced lymphocytolysis. In: Thompson EB, Lippman ME (eds) Steroid Receptors and the Management of Cancer, Vol II. CRC Press, Boca Raton, FL, pp 87–98Google Scholar
  73. 73.
    Harmon JM, Norman MR, Fowlkes BJ, Thompson EB (1979) Dexamethasone induces irreversible G, arrest and death of a human lymphoid cell line. J Cell Physiol 98:267–278Google Scholar
  74. 74.
    Harmon JM, Schmidt TJ, Thompson EB (1982) Defective steroid receptors in a glucocorticoid resistant clone of a human leukemic cell line. In: Leavitt WW (ed) Hormones and Cancer. Plenum, New York, pp 301–313Google Scholar
  75. 75.
    Rabin H, Hopkins RF, Ruscetti FW, Neubauer RH, Brown RL, Kawakami TG (1981) Spontaneous release of a factor with properties of T cell growth factor from a continuous line of primate tumor T Cells. J Immunol 127:1852–1856Google Scholar
  76. 76.
    Galili U, Peleg A, Milner Y, Galili N (1984) Be13, a human T-leukemia cell line highly sensitive to dexamethasone-induced cytolysis. Cancer Res 44:4594–4601Google Scholar
  77. 77.
    Galili U, Prokocimer M, Izak G (1980) The in vitro sensitivity of leukemic and normal leukocytes to hydrocortisone induced cytolysis. Blood 56:1077–1081Google Scholar
  78. 78.
    Goldin A, Sandberg J, Henderson E, Newman J, Frei E, Holland J (1971) The chemotherapy of human and animal acute leukemia. Cancer Chemother Rep 55:309–507Google Scholar
  79. 79.
    McPartland RP, Milholland RJ, Rosen F (1977) Nuclear binding of steroid-receptors complex to lymphosarcoma P1798 resistant and sensitive cells and effect of concanavalin A on receptor levels. Cancer Res 37:4256–4260Google Scholar
  80. 80.
    Wood KM, Thompson EA Jr (1984) Isolation and characterization of lymphosarcoma P1798 variants selected for resistance to the cytolytic effects of glucocorticoids in vivo and in culture. Mol and Cell Endocrin 37:169–180Google Scholar
  81. 81.
    Johnson DM, Newby RF, Bourgeois S (1984) Membrane permeability as a determinant of dexamethasone resistance in murine thymoma cells. Cancer Res 44:2435–2440Google Scholar
  82. 82.
    Gasson JC, Ryden T, Bourgeois S (1983) Role of de novo DNA methylation in the glucocorticoid resistance of a T-lymphoid cell line. Nature 302:621–623Google Scholar
  83. 83.
    Gasson JC, Bourgeois S (1983) A new determinant of glucocorticoid sensitivity in lymphoid cell lines. J Cell Biol 96:409–415Google Scholar
  84. 84.
    Davis JM, Chan AK, Thompson EA Jr (1980) Nonmutational alteration in glucocorticoid sensitivity of lymphosarcoma P1798. J Natl Cancer Inst64, 55–62Google Scholar
  85. 85.
    Danielsen M, Stallcup MR (1984) Down-regulation of glucocorticoid receptors in mouse lymphoma cell variants. Molec Cell Biol 4:449–453Google Scholar
  86. 86.
    Schmidt TJ, Harmon JM, Thompson EB (1980) ‘Activation-labile’ glucocorticoid-receptor complexes of a steroid-resistant variant of CEM-C7 human lymphoid cells. Nature 286:507–510Google Scholar
  87. 87.
    Harmon JM, Schmidt TJ, Thompson EB (1984) Molybdatesensitive and molybdate-resistant activation-labile glucocorticoid receptor mutants of the human lymphoid cell line CEM-C7. J Steroid Biochem 21:227–236Google Scholar
  88. 88.
    Stevens J, Stevens Y, Hauabenstock H (1983) Molecular basis of glucocorticoid resistance in experimental and human leukemia. In: Litack G (ed) Biochemical Actions of Hormones, Vol X. Academic Press, New York, pp 383–346Google Scholar
  89. 89.
    Doerfler W (1983) DNA methylation and gene activity. Ann Rev Biochem 52:93–124Google Scholar
  90. 90.
    Creusot F, Acs G, Christman JK (1982) Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-Azacytidine and 5-aza-2′-deoxycytidine. J Biol Chem 257:2041–2048Google Scholar
  91. 91.
    Clough DW, Kunkel LM, Davidson RL (1982) 5-azacytidine-induced reactivation of a herpes simplex thymidine kinase gene. Science 216:70–73Google Scholar
  92. 92.
    Mermod J-J, Bourgeois S, Defer N, Crepin M (1983) Demethylation and expression of murine mammary tumor proviruses in mouse thymoma cell lines. Proc Natl Acad Sci USA 80:110–114Google Scholar
  93. 93.
    Ley TJ, DeSimone J, Anagnou NP, Keller GH, Humphries K, Turner PH, Young NS, Heller P, Nienhuis AW (1982) 5-azacytidine selectively increasesγ-globin synthesis in a patient withβ + thalassemia. New Eng J Med 307:1469–1475Google Scholar
  94. 94.
    Nawata H, Sekiya K, Higuchi K, Yanase T, Kata K, Ibayashi H (1984) Thermolabile and activation-labile glucocorticoid receptor of cultured skin fibroblast in the patient of glucocorticoid resistance syndrome. Abstracts, 7th International Congress of Endocrinology. Excerpta Medica, Amsterdam, Oxford Princeton, p 1063Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • E. B. Thompson
    • 1
  • J. R. Smith
    • 3
  • S. Bourgeois
    • 3
  • J. M. Harmon
    • 4
  1. 1.Laboratory of Biochemistry, National Cancer InstituteNational Institutes of HealthBethesda
  2. 2.Department of Human Biological Chemistry and GeneticsThe University of Texas Medical BranchGalveston
  3. 3.Regulatory Biology LaboratoryThe Salk InstituteSan Diego
  4. 4.Department of PharmacologyUniformed Services University of the Health SciencesBethesda

Personalised recommendations