Skip to main content

Glucocorticoid Antagonists and the Role of Glucocorticoids at the Resting and Stress State

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 245))

Abstract

Glucocorticoids act on almost all organs and tissues. Their levels are rarely constant, showing both pronounced circadian variations and/or a rise during stressful situations. It is thought that glucocorticoids evoke an adaptation to stress via a variety of mechanisms including mobilization of fuel for metabolism, enhancement of cardiovascular function, and production of euphoria or behavioral activation. Glucocorticoids also suppress the immune system. It has been argued that this effect helps prevent autoimmune activation following “fight or flight” situations that result in trauma and inflammation.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover 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. A. S. Munck, P. M. Guyre, N. J. Holbrook, Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endo. Rev., 5, 25 (1984).

    Google Scholar 

  2. A. S. Munck, P. M. Guyre, Glucocorticoid physiology, pharmacology and stress, in: “Steroid Hormone Resistance”, G. P. Chrousos, D. L. Loriaux, M. B. Lipsett, eds., Plenum Press, New York, 81 (1986).

    Chapter  Google Scholar 

  3. R. J. Flower, The mediators of steroid action, Nature. 320:20 (1986).

    Article  PubMed  CAS  Google Scholar 

  4. L. Laue, S. Kawai, D. Brandon, D. L. Loriaux, G. P. Chrousos, Glucocorticoid and glucocorticoid antagonist effects on the inflammatory response, Ped. Res., 20:296A (1986).

    Article  Google Scholar 

  5. L. Laue, S. Kawai, D. Brandon, D. Brightwell, K. Barnes, R. Knazek, D. L. Loriaux, G. P. Chrousos, Receptor-mediated effects of glucocorticoids on inflammation: Enhancement of the inflammatory response with a glucocorticoid antagonist, J. Steroid Biochem. (in press) (1988).

    Google Scholar 

  6. F. J. Flower, L. Parente, P. Persico, J. A. Salmon, A comparison of the acute inflammatory response in adrenalectomized and sham-operated rats, Br. J. Pharmac. 87:57 (1986).

    Article  CAS  Google Scholar 

  7. M. DiRosa, Role in inflammation of glucocorticoid-induced phospholipase inhibitory proteins, Prog. Biochem. Pharmacol. 20:55 (1985).

    CAS  Google Scholar 

  8. B. Rothhut, F. Russo-Marie, Novel concepts in the mode of action of antiinflammatory steroids, Agents Actions Suppl. 14:171 (1984).

    PubMed  CAS  Google Scholar 

  9. A. S. Fauci, Glucocorticosteroid therapy: Mechanisms of action and clinical considerations, Ann. Int. Med. 84:304 (1976).

    Article  PubMed  CAS  Google Scholar 

  10. H. C. Stevenson, A. S. Fauci, The effects of glucocorticoids and other hormones on inflammatory and immune responses, in: “Cellular Functions in Immunity and Inflammation”, J. J. Oppenheim, D. L. Rosenstreich, M. Potter, eds., Elsevier Co., New York, 431 (1984).

    Google Scholar 

  11. G. Weissman, Pathways of arachiodonate oxidation to prostaglandins and leukotrienes, Seminars in Arthritis and Rheumatology. 13:123s (1983).

    Article  Google Scholar 

  12. G. Weissman, Prostaglandins in acute inflammation, Current Concepts Monographs, Upjohn Co., Kalamazoo, Michigan, 1 (1980).

    Google Scholar 

  13. B. Samuelson, Mediators of immediate hypersensitivity reactions and inflammation, Science. 220:568 (1983).

    Article  Google Scholar 

  14. J. J. Oppenheim, M. Potter, Immunity and inflammation, in: “Cellular Functions in Immunity and Inflammation”, J. J. Oppenheim, D. L. Rosenstreich, M. Potter, eds., Elsevier Co., New York, 1 (1984).

    Google Scholar 

  15. D. Feldman, The role of hormone receptors in the action of adrenal steroids. Ann. Rev. Med.. 26:83 (1975).

    Article  PubMed  CAS  Google Scholar 

  16. G. G. Rousseau, J. D. Baxter, Glucocorticoid hormone action, in: “Monographs in Endocrinology”, J. D. Baxter, G. G. Rousseau, eds., Springer-Verlag, Germany, 12:49 (1979).

    Google Scholar 

  17. G. G. Rousseau, Structure and regulation of the glucocorticoid receptor, Mol Cell Endocrinol.. 38:1 (1984).

    Article  PubMed  CAS  Google Scholar 

  18. B. W. O’Malley, U. T. Schrader, M. J. Tsai, Molecular actions of steroid hormones. in: “Steroid Hormone Resistance”, G. P. Chrousos, D. L. Loriaux, M. B. Lipsett, eds., Plenum Press, New York, 1 (1986).

    Chapter  Google Scholar 

  19. R. J. Flower, G. J. Blackwell, Antiinflammatory steroid induced biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation, Nature. 278:456 (1979).

    Article  PubMed  CAS  Google Scholar 

  20. R. Carnuccio, M. DiRosa, P. Persico, Hydrocortisone induced inhibition of prostaglandin biosynthesis in rat leukocytes, Br. J. Pharm., 68:14 (1980).

    Article  CAS  Google Scholar 

  21. A. Danon, G. Assouline, Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis, Nature, 273:552 (1978).

    Article  PubMed  CAS  Google Scholar 

  22. M. DiRosa, P. Persico, Mechanism of inhibition of prostaglandin biosynthesis by hydrocortisone in rat leukocytes. Br. J. Pharm., 66, 161 (1979).

    Article  CAS  Google Scholar 

  23. G. J. Blackwell, R. Carnuccio, M. DiRosa, R. J. Flower, L. Parente, P. Persico, Macrocortin: A polypeptide causing the antiphospholipase effects of glucocorticoids. Nature, 287, 147 (1980).

    Article  PubMed  CAS  Google Scholar 

  24. J. F. Cloix, O. Colard, B. Rothhut, F. Russo-Marie, Characterization and partial purification of “renocortins”: two polypeptides formed in renal cells causing the anti-phospholipase-like action of glucocorticoids. Br. J. Pharm.. 79:313 (1983).

    Article  CAS  Google Scholar 

  25. B. P. Wallner, R. J. Mattaliano, C. Hession, R. L. Cate, R. Tizard, L. K. Sinclair, C. Fueller, E. P. Chow, J. L. Browning, K. L. Ramachandran, R. B. Pepinsky, Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential antiinflammatory activity. Nature, 320, 77 (1986).

    Article  PubMed  CAS  Google Scholar 

  26. G. J. Blackwell, R. Carnuccio, M. DiRosa, R. J. Flower, C. J. Langham, L. Parente, P. Persico, N. C. Russell-Smith, D. Stone, Glucocorticoids induce the formation and release of antiinflammatory and antiphospholipase proteins into the peritoneal cavity of the rat. Br. J. Pharm., 76, 185 (1982).

    Article  CAS  Google Scholar 

  27. F. Hirata, E. Schiffman, K. Venkatasubramanian, D. Salomon, J. Axelrod, A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc. Nat. Acad. Sci. USA. 77:2533 (1980).

    Article  PubMed  CAS  Google Scholar 

  28. F. Hirata, M. Notsu, M. Iwata, L. Parente, M. DiRosa, R. J. Flower, Identification of several species of phospholipase inhibitory proteins by radioimmunoassay for lipomodulin. Biochem. Biophys. Res. Commun.. 109:223 (1982).

    Article  PubMed  CAS  Google Scholar 

  29. B. Rothhut, F. Russo-Marie, J. Wood, M. DiRosa, R. J. Flower, Further characterization of the glucocorticoid-induced antiphospholipase protein “renocortin”. Biochem. Biophys. Res. Commun., 117, 878 (1983).

    Article  PubMed  CAS  Google Scholar 

  30. K. S. Huang, B. P. Wallner, R. J. Mattaliano, B. Tizard, C. Burne, A. Frey, C. Hession, P. McGray, K. L. Sinclair, E. P. Chow, J. L. Browning, K. L. Ramachandran, J. Tang, J. E. Smart, R. B. Pepinsky, Two human 35 kilodalton inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase, Cell. 46:191 (1986).

    Article  PubMed  CAS  Google Scholar 

  31. A. H. Tashjian, E. F. Coelkel, J. McDonough, L. Levine, Hydrocortisone inhibits prostaglandin production by mouse fibrosarcoma cells, Nature, 258:739 (1975).

    Article  PubMed  CAS  Google Scholar 

  32. I. Jung-Testas, E. E. Baulieu, Inhibition of glucocorticosteroid action in cultured L-929 mouse fibroblasts by RU 486, a new antiglucocortico-steroid receptor. Exp. Cell Res.. 147:177 (1983).

    Article  PubMed  CAS  Google Scholar 

  33. N. Oliver, R. F. Newby, L. T. Furcht, S. Bourgeois, Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts, Cell. 33:287 (1983).

    Article  PubMed  CAS  Google Scholar 

  34. M. N. Chobert, R. Baronki, J. Finidori, M. Aggerbeck, J. Hanoume, D. Philibert, R. Deraedt, Antiglucocorticoid properties of RU 38486 in a differentiated hepatoma cell line, Biochem. Pharmacol., 43:3481 (1983).

    Article  Google Scholar 

  35. S. Chasserot-Golaz, G. Beck, An approach to the mechanism of the potent antiglucocorticoid: 17 beta-hydroxy-11 beta-4-dimethylaminophenyl 17-alpha-propynyl-estra-4,9-diene-3-one, J. Steroid Biochem., 21:585 (1984).

    Article  PubMed  CAS  Google Scholar 

  36. E. Coezy, J. Bouhnik, E. Clauser, F. Pinet, M. Philippe, J. Menard, P. Carvol, Effects of glucocorticoids and antiglucocorticoids on angiotensinogen production by hepatoma cells in culture. In vitro. 20:528 (1984).

    Article  PubMed  CAS  Google Scholar 

  37. L. Proux-Ferland, J. Cote, D. Philibert, R. Deraedt, Potent antiglucocorticoid activity of RU 38486 on ACTH secretion in vitro and in vivo in the rat, 6th International Congress on Hormonal STeroids, J Steroid Biochem., 17:xvii, (Abstr), 80 (1982).

    Google Scholar 

  38. S. J. Lamberts, E. G. Bons, P. Uitterlinden, Studies on the glucocorticoid receptor blocking action of RU 38486 in cultured ACTH-secreting human pituitary tumor cells and normal rat pituitary cells. Acta. Endocrinological., 109, 64 (1985).

    CAS  Google Scholar 

  39. B. Groner, H. Ponta, U. Rahmsclore, P. Herrlichl, M. Pfahll, N. E. Hynes, Glucocorticoid hormone interaction with cloned proviral DNA of mouse mammary tumor virus, J. Steroid Biochem., 20:95 (1984).

    Article  PubMed  CAS  Google Scholar 

  40. S. Bourgeois, M. Pfahl, E. E. Baullieu, DNA binding properties of glucocorticosteroid receptors bound to the steroid antagonist RU 486, Embo. J. 3:751 (1984).

    PubMed  CAS  Google Scholar 

  41. D. Duval, S. Surant, F. Homo-Delarche, Effects of antiglucocorticoids on dexamethasone-induced inhibition of uridine incorporation and cell lysis in isolated mouse thymocytes, J. Steroid Biochem., 20:283 (1984).

    Article  PubMed  CAS  Google Scholar 

  42. D. Emile, P. Galanaud, E. E. Baulier, J. Dormont, Inhibition of in vitro immunosuppressive effects of glucocorticosteroids by a competitive antagonist RU 486, Immunol. Letters. 9:183 (1984).

    Article  Google Scholar 

  43. D. A. Henderson, G. Neef, C. Bengston, M. Tobert, The antiprogestin and antiglucocorticoid activities of 11-beta substituted steroids can be separated, 7th International Congress of Endocrinology, Excerpta Medica International Congress Series 652, (Abstr), 1457 (1984).

    Google Scholar 

  44. D. Philibert, R. Deraedt, G. Teutsch, RU 38486: A potent antiglucocorticoid in vivo. Internat. Congress of Pharmacology, Tokyo, (Abst), 1463 (1981).

    Google Scholar 

  45. D. Philibert, RU 38486: An original multifaceted antihormone in vivo. in: “Adrenal Steroid Antagonism”, M. K. Agarwal, ed., Walter de Gruyter and Co., New York, 77 (1984).

    Google Scholar 

  46. T. Gagne, M. Pons, D. Philibert, RU 486 a potent antiglucocorticoid in vivo and in vitro. J. Steroid Biochem.. 23:247 (1985).

    Article  PubMed  CAS  Google Scholar 

  47. R. C. Gaillard, A. Riondel, W. Herrman, A. F. Muller, E. E. Baulieu, RU 486: A steroid with antiglucocorticosteroid activity that only disinhibits the human pituitary-adrenal system at a specific time of day, Proc. Nat. Acad. Sci., 81:3879 (1984).

    Article  PubMed  CAS  Google Scholar 

  48. R. D. Gaillard, D. Poffett, A. M. Riondel, J. H. Saurat, RU 486 inhibits peripheral effects of glucocorticoids in human. J. Clin. Endocrinol. Metab., 61, 1009 (1985).

    Article  PubMed  CAS  Google Scholar 

  49. X. Bertagna, C. Bertagna, J. P. Luton, J. M. Husson, F. Girard, The new steroid analogue RU 486 inhibits glucocorticoid action in man, J. Clin. Endocrinol. Metabol., 59:25 (1984).

    Article  CAS  Google Scholar 

  50. L. K. Nieman, E. E. Baulieu, D. Healy, R. Gaillard, G. Schaison, D. Shoupe, D. L. Loriaux, R. Udelsman, G. P. Chrousos, Clinical applications of a glucocorticoid and progesterone antagonist, Endocrine Reviews, (submitted) (1987).

    Google Scholar 

  51. J. P. Grunfeld, L. Eloy, A. M. Moura, D. Ganeval, B. Ramos-Grendo, M. Worcel, Effects of antiglucocorticoids on glucocorticoid hypertension in the rat, Hypertension, 7:292 (1984).

    Article  Google Scholar 

  52. D. L. Healy, G. P. Chrousos, H. M. Schulte, R. F. Williams, P. W. Gold, E. E. Baulieu, G. D. Hodgen, Pituitary and adrenal responses to the antiprogesterone and antiglucocorticoid steroid RU 486 in primates. J. Clin. Endocrinol. Metabol., 57, 863 (1983).

    Article  CAS  Google Scholar 

  53. D. L. Healy, G. P. Chrousos, H. M. Schulte, P. W. Gold, G. P. Hodgen, Increased adrenocorticotropin, cortisol and arginine vasopressin secretion in primates after the antiglucocorticoid steroid RU 486: dose response relationships, J. Clin. Endocrinol. Metabol., 60:1 (1985).

    Article  CAS  Google Scholar 

  54. M. Moguilewsky, D. Philibert, Biochemical profile of RU 486, in: “The Antiprogestin Steroid RU 486 and Human Fertility Control”, E. E. Baulieu, S. J. Segal, eds., Plenum Press, New York, 87 (1985).

    Chapter  Google Scholar 

  55. S. Tsurufuji, S. Hiroshi, K. R. Min, K. Ohuchi, Difference in the anti-inflammatory effects of indomethacin between acute and chronic states of carrageenin-induced inflammation, J. Pharm. Dyn., 1:8 (1978).

    Article  CAS  Google Scholar 

  56. R. Deraedt, B. Vannier, R. Fournex, Toxicological study on RU 486, in: “The Antiprogestin Steroid RU 486 and Human Fertility Control”, E. E. Baulieu, S. J. Segal, eds., Plenum Press, New York, 123 (1985).

    Chapter  Google Scholar 

  57. L. Laue, G. P. Chrousos, W. Gallucci, P. Munson, K. Barnes, D. L. Loriaux, L. K. Nieman, G. Schaison, The antiprogestin and antiglucocorticoid steroid RU 486 inhibits the ACTH response to ovine corticotropin releasing hormone in man, J. Clin. Endo. Metabol., 66:290 (1988).

    Article  CAS  Google Scholar 

  58. S. Tsurufuji, K. Sugio, F. Takemasa, The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone, Nature. 280:408 (1979).

    Article  PubMed  CAS  Google Scholar 

  59. S. Tsurufuji, A. Kurihara, F. Ojima, Mechanisms of anti-inflammatory action of dexamethasone: Blockade by hydrocortisone mesylate and actinomycin D of the inhibitory effect of dexamethasone on leukocyte infiltration in inflammatory sites. J. Pharm. Exper. Ther., 229, 237 (1983).

    Google Scholar 

  60. S. Tsurufuji, S. Kazuo, F. Takemasa, S. Yoshizawa, Blockade by antiglucocorticoids, actinomycin D and cyclohnexamide of anti-inflammatory action of dexamethasone against bradykinin, J. Pharm. Exper. Ther. 212:225. (1979).

    Google Scholar 

  61. M. Stein, S. Schleifer, S. Keller, The role of the brain and neuro-endocrine system in immune regulation: Potential links to neoplastic disease. in: “Biological Mediators of Behavior and Disease”, S. Levy, ed., Elsevier, Co, New York, 147 (1982).

    Google Scholar 

  62. J. Axelrod, T. D. Reisine, Stress hormones; their interaction and regulation, Science. 224:452 (1984).

    Article  PubMed  CAS  Google Scholar 

  63. M. Stein, S. Keller, S. Schleifer, Stress and immunomodulation: The role of depression and neuroendocrine function, J. Immunol., 135:827s (1985).

    Google Scholar 

  64. Y. Shavit, G. Terman, F. Martin, J. Lewis, J. Liebeskind, R. Gale, Stress, opioid peptides, the immune system and cancer, J. Immunol., 135:834s (1985).

    Google Scholar 

  65. A. Manjan, M. Collector, Stress-induced modulation of the immune response, Science. 196:307 (1977).

    Article  Google Scholar 

  66. J. V. Fahey, P. M. Guyre, A. Munck, Mechanisms of antiinflammatory actions of glucocorticoids, Adv. Inflamm. Res., 2:21 (1981).

    CAS  Google Scholar 

  67. R. Carnuccio, M. DiRosa, R. J. Flower, A. Pinto, The inhibition by hydrocortisone of prostaglandin biosynthesis in rat peritoneal leukocytes is correlated with intracellular macrocortin levels, Br. J. Pharm., 74:322 (1981).

    Article  CAS  Google Scholar 

  68. L. Laue, J. Peacock, D. Brandon, W. Gallucci, G. Cutler, D. L. Loriaux, G. P. Chrousos, J. Norton, Glucocorticoid receptor-mediated effects on rat fibrosarcoma growth, Cancer Res., 48:2703 (1988).

    PubMed  CAS  Google Scholar 

  69. L. Laue, K. Barnes, T. Fleisher, Effects of chronic hypercortisolism and hypocortisolism on leukocyte subpopulations, Endo. Soc. 70:112A (1988).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer Science+Business Media New York

About this chapter

Cite this chapter

Laue, L., Loriaux, D.L., Chrousos, G.P. (1988). Glucocorticoid Antagonists and the Role of Glucocorticoids at the Resting and Stress State. In: Chrousos, G.P., Loriaux, D.L., Gold, P.W. (eds) Mechanisms of Physical and Emotional Stress. Advances in Experimental Medicine and Biology, vol 245. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2064-5_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-2064-5_18

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-2066-9

  • Online ISBN: 978-1-4899-2064-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics