Skip to main content

Glucocorticoid Resistance and Hypersensitivity

  • Chapter
Hormone Resistance Syndromes

Part of the book series: Contemporary Endocrinology ((COE,volume 14))

  • 147 Accesses

Abstract

Target tissue resistance to steroid hormones implies inability or decreased sensitivity of the tissues to respond to these hormones (1,2). This resistance can be transient or permanent, incomplete (partial) or complete, and compensated or noncompensated. Two patients, a father and a son, with long-term “hypercortisolism” not associated with clinical manifestations of Cushing’s syndrome were described by Vingerhoeds et al. in 1976 (reviewed in ref. 3). We studied this family extensively as well as several other families with the syndrome of familial glucocorticoid resistance reported since. Two New World primate species, the squirrel monkey (Saimiri sciureus) and the marmosets Callithrix argentatus and jacchus, and Sanguinus oedipus, also have elevated plasma cortisol values, when compared to Old World primates, without any evidence of glucocorticoid hormone excess (2). In addition, these New World primates have elevated plasma levels of aldosterone, progesterone, testosterone, and 1,25-(OH)2-vitamin D, suggesting that these species have generalized or “pan-steroid” hormone resistance. Two other New World animal species also have glucocorticoid resistance: the guinea pig, for which there is considerable amount of information available (4), and the little-studied prairie vole Microtus ochrogaster, an interesting monogamous rodent with many features reminis-cent of the social primate Callithrix jacchus jacchus (5).

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chrousos GP, Loriaux DL, Gold PW. (eds.) Mechanisms of physical and emotional stress. In: Advances in Experimental Medicine and Biology, vol. 245, Plenum, New York, 1988.

    Google Scholar 

  2. Chrousos GP, Loriaux DL, Lipsett MB. (eds.) Steroid hormone resistance: mechanisms and clinical aspects. In: Advances in Experimental Medicine and Biology, vol. 196, Plenum, New York, 1986.

    Google Scholar 

  3. Chrousos GP, Detera-Wadleigh S, Karl M. Syndromes of glucocorticoid resistance. Ann Int Med 1993; 119: 113–1124.

    Google Scholar 

  4. Keightley MC, Fuller PJ. Cortisol resistance and the guinea pig glucocorticoid receptor. Steroids 1995; 60: 87–92.

    Article  PubMed  CAS  Google Scholar 

  5. Taymans SE, De Vries AC, De Vries MB, Nelson RJ, Friedman TC, Castro M, et al. The hypothalamic-pituitary-adrenal axis of Prairie Voles (Microtus Ochrogaster): Evidence for target tissue glucocorti-coid resistance. Comp Endocrinol 1997; 106: 48–61.

    Article  CAS  Google Scholar 

  6. DeKloet ER. Brain corticosteroid receptor balance and homeostatic control. Frontiers Neuroendocrinol 1991; 12: 95–164.

    Google Scholar 

  7. Evans RM. The steroid and thyroid hormone receptor superfamily Science 1988; 240: 889–895.

    CAS  Google Scholar 

  8. Ulman KS, Powers MA, Forbes DJ. Nuclear export receptors: from importin to exportin. Cell 1997; 90: 967–970.

    Article  Google Scholar 

  9. Chakravarti D, LaMorte VJ, Nelson MC, Nakajima T, Shulman IG, Juguilon H, et al. Role of CBP/P300 in nuclear receptor signaling. Nature 1996; 383: 99–103.

    Article  PubMed  CAS  Google Scholar 

  10. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, et al. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1986; 85: 403–414.

    Article  Google Scholar 

  11. Onate SA, Tsai SY, Tsai MJ, O’Mallay BW. Sequence and characterization of a co-activator for the steroid hormone receptor superfamily. Science 1995; 270: 1354–1357.

    Article  PubMed  CAS  Google Scholar 

  12. Hong H, Kohli K, Trivedi A, Johnson DL, Stallcup MR. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci USA 1996; 93: 4948–4952.

    Article  PubMed  CAS  Google Scholar 

  13. Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, et al. The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 1997; 387: 677–684.

    Article  PubMed  CAS  Google Scholar 

  14. Xu J, Qiu Y, De Mayo FJ, Tsai SY, Tsai MJ, O’Malley BW. Partial hormone resistance in mice with disruption of the steroid receptor co-activator-1 (SRC-1) gene. Science 1998; 279: 1922–1925.

    Article  PubMed  CAS  Google Scholar 

  15. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid Therapy of Immune-Related Diseases: Basic and Clinical Correlates. Ann Intern Med 1993; 119: 1198–1208.

    Article  PubMed  CAS  Google Scholar 

  16. Schule R, Rangarajan P, Kliewer S, Ransone LJ, Bolado J, Yang N, et al. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 1990; 62: 1217–1226.

    Article  PubMed  CAS  Google Scholar 

  17. Ray A, Prefontaine KE. Physical association and functional antagonism between the p65 subunit of transcription factor NF-KB and the glucocorticoid receptor. Proc Natl Acad Sci USA 1994; 91: 752–756.

    Article  PubMed  CAS  Google Scholar 

  18. Caldenhoven E, Liden J, Wissnik S, Van de Stolpe A, Raaijmakers J, Koenderman L, et al. Negative cross talk between rel A and glucocorticoid receptor. a possible mechanism for the antiinflammatory action of glucocorticoids. Mol Endocrinol 1995; 9: 401–412.

    Article  PubMed  CAS  Google Scholar 

  19. Scheinman RI, Gualberto A, Jewell CM, Aldowski JA, Baldwin AS Jr. Characterization of mechanisms involved in transrepression of NF-KB by activated glucocorticoid receptors. Mol Cell Biol 1995; 15: 943–953.

    PubMed  CAS  Google Scholar 

  20. Imai E, Miner JN, Mitchell JA, Yamamoto KR, Granner DK. Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids. J Biol Chem 1993; 268: 5353–5356.

    PubMed  CAS  Google Scholar 

  21. Nishio Y, Isshiki H, Kishimoto T, Akira S. A nuclear factor for interleukin-6 expression (NF-IL6) and the glucocorticoid receptor synergically activate transcription of the rat al-acid glycoprotein gene via direct protein-protein interaction. Mol Cell Biol 1993; 13: 1854–1862.

    PubMed  CAS  Google Scholar 

  22. Stocklin E, Wissler M, Gouilleux F, Groner B. Functional interactions between Stat 5 and the glucocorti-coid receptor. Nature 1996; 383: 726–728.

    Article  PubMed  CAS  Google Scholar 

  23. Encio IJ, Detera-Wadleigh SD. The genomic structure of the human glucocorticoid receptor. J Biol Chem 1991; 266: 7182–7188.

    PubMed  CAS  Google Scholar 

  24. Nobukumi Y, Smith CL, Hager GL, Detera-Wadleigh SD. Characterization of the human glucocorticoid receptor promoter. Biochemistry 1995; 34: 8207–8214.

    Article  Google Scholar 

  25. Bamberger CM, Bamberger AM, De Castro M, Chrousos GP. Glucocorticoid receptor-beta, a potential endogenous inhibitor of glucocorticoid action in humans. J Clin Invest 1995; 95: 2435–2441.

    Article  PubMed  CAS  Google Scholar 

  26. Castro M, Elliot S, Kino T, Bamberger C, Karl M, Webster E, et al. The non-ligand binding B-isoform of the human glucocorticoid receptor (hGRb): tissue levels, mechanism of action, and potential physi-ologic role. Mol Med 1996; 5: 1076–1551.

    Google Scholar 

  27. De Lange P, Koper JW, Huizenga NATM, Brinkman AO, De Jong FH, Karl M, et al. Differential hormone-dependent transcriptional activation and repression by naturally occurring human glucocor-ticoid receptor variants. Mol Endocrinol 1997; 11: 1156–1164.

    Article  PubMed  Google Scholar 

  28. Oackley RH, Webster JC, Sar M, Parker CR, Cidlowski JA. Expression and subcellular distribution of the 13 isoform of the human glucocorticoid receptor. Endocrinology 1997; 138: 5028–5038.

    Article  Google Scholar 

  29. Leung DYM, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, et al. Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor 13. J Exp Med 1997; 186: 1567–1574.

    Article  PubMed  CAS  Google Scholar 

  30. Vamvakopoulos NC, Fukuhara K, Patchev VK, Chrousos GP. Effect of single and repeated immobilization stress on the heat shock protein (HSP) 70/90 system in the rat: glucocorticoid-independent, reversible reduction of HSP90 in the liver and spleen. Neuroendocrinology 1993; 57: 1057–1065.

    Article  PubMed  CAS  Google Scholar 

  31. Patchev VK, Brady LS., Karl M, Chrousos GP. Gene expression of HSP90 and glucocorticoid receptors in the brain: evidence for coordinate regulation by adrenal steroid levels in vivo. Cell Mol Endocrinol 1994; 103: 57–64.

    Article  CAS  Google Scholar 

  32. Auphan N, Didonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappaB activity through induction of I kappa B synthesis. Science 1995; 270: 283–286.

    Article  Google Scholar 

  33. Watt GCM, Harrap SB, Foy CJW, Holton DW, Edwards HV, Davidson HR, et al. Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four corners approach to the identification of genetic determinants of blood pressure. J Hypertens 1992; 10: 473–482.

    Article  PubMed  CAS  Google Scholar 

  34. Weaver JV, Hitman GA, Kopelman PG. An association between a bcpl restriction fragment length polymorphism of the glucocorticoid receptor locus and hyperinsulinaemia in obese women. J Mol Endocrinol 1992; 9: 295–300.

    Article  PubMed  CAS  Google Scholar 

  35. Hurley D, Accilli D, Stratakis C, Karl M, Vamvakopoulos N, Rorer E, et al. Mutation of the glucocorticoid receptor gene in familial glucocorticoid resistance. J Clin Invest 1991; 87: 680–686.

    Article  PubMed  CAS  Google Scholar 

  36. Koper JW, Stolk RP, de Lange P, Huizenga NATM, Molijn GJ, Pols HAP, et al. Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum Genet 1997; 99: 663–668.

    Article  PubMed  CAS  Google Scholar 

  37. Karl M, Lamberts SW, Detera-Wadleigh S, Encio IJ, Stratakis CA, Hurley DM, et al. Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. J Clin Endocrinol Metab 1993; 76: 683–689.

    Article  PubMed  CAS  Google Scholar 

  38. Nathan DF, Lindquist S. Mutational analysis of HSP 90 function: interactions with a steroid receptor and a protein kinase. Mol Cell Biol 1995; 15: 3917–3925.

    PubMed  CAS  Google Scholar 

  39. Kang KI, Devin J, Cadepond F, Jibard N, Guiochon-Mantel A, Baulieu EE, et al. In vivo functional protein-protein interaction: nuclear targeted HSP 90 shifts cytoplasmic steroid receptors into the nucleus. Proc Natl Acad Sci USA 1994; 91: 340–344.

    Article  PubMed  CAS  Google Scholar 

  40. Karl M, Lamberts SW, Koper JW, Katz DA, Huizenga NE, Kino T, et al. Cushing’s disease preceded by generalized glucocorticoid resistance: clinical consequences of a novel, dominant-negative glucocorticoid receptor mutation. Proc Assoc Am Phys 1996; 108: 296–307.

    PubMed  CAS  Google Scholar 

  41. Strasser-Wozak EMC, Hattmannstoffer R, Hala M, HartmanBL, Fiegl SG, Kofler R. Splice site mutation in the glucocorticoid receptor gene causes resistance to glucocorticoid-induced apoptosis in a human acute leukemic cell line. Cancer Res 1995; 55: 348–353.

    PubMed  CAS  Google Scholar 

  42. Powers JH, Hillman AG, Tang DC, Harmon JM. Cloning and expression of mutant glucocorticoid receptors from glucocorticoid-sensitive and resistant human leukemic cells. Cancer Res 1993; 53: 3877–3879.

    Google Scholar 

  43. Moalli PA, Pillay S, Krett NL, Rosen ST. Alternative spliced glucocorticoid receptor messenger RNAs in glucocorticoid-resistant human myeloma cells. Cancer Res 1993; 53: 3877–3879.

    PubMed  CAS  Google Scholar 

  44. Karl M, Von Wichert G, Kempter E, Katz DA, Reincke M, Monig H, et al. Nelson’ s syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene. J Clin Endocrinol Metab 1996; 81: 124–129.

    Article  PubMed  CAS  Google Scholar 

  45. Huizenza NATM, de Lange P, Koper JW, Clayton RN, Farrel WE, van der Lely AJ, et al. Human adrenocorticotropin-secreting pituuitary adenomas show frequent loss of heterozygosity at the glucocorticoid receptor gene locus. J Clin Endocrinol Metab 1998; 83: 917–921.

    Article  Google Scholar 

  46. Sher ER, Leung DVM, Surs W, Kam JC, Zieg G, Kamada AK, Szefler SJ. Steroid-resistant asthma. cellular mechanisms contributing to inadequate response to glucocorticoid therapy. J Clin Invest 1994; 93: 33–39.

    Article  PubMed  CAS  Google Scholar 

  47. Schlaghecke R, Kornely E., Wollenhaupt J, Specker C. Glucocorticoid receptors in rheumatod arthritis. Arthritis Rheum 1994; 35: 740–744.

    Article  Google Scholar 

  48. Schlaghecke R, Beuscher D, Kornely E, Specker C. Effects of glucocorticoids in rheumatoid arthritis. Arthritis Rheum 1994; 37: 1127–1131.

    Article  PubMed  CAS  Google Scholar 

  49. Costas M, Trapp T, Pereda MP, Sauer J, Rupprecht R, Nahmod VE, et al. Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoïds. J Clin Invest 1996; 98: 1409–1416.

    Article  PubMed  CAS  Google Scholar 

  50. Rakasz E, Gal A, Biro J, Balas G, Falus A. Modulation of glucocorticosteroid binding in human lymphoid, monocytoid and hepatoma cell lines by inflammatory cytokines IL-1f3, IL-6 and TNFa. Scand J Immunol 1993; 37: 684–689.

    Article  PubMed  CAS  Google Scholar 

  51. Salkowski CA, Vogel SN. IFNy mediates increased glucocorticoid receptor expression in murine mac-rophages. J Immunol 1992; 148: 2770–2777.

    PubMed  CAS  Google Scholar 

  52. Kam JC, Szefler SJ, Surs W, Sher ER, Leung DY. Combination of IL-2 and IL-4 reduces glucocorticoïd receptor-binding affinity and T cell response to glucocorticoïds. J Immunol 1993; 7: 3460–3466.

    Google Scholar 

  53. Spahn DS, Szefler J, Surs W, Doherty DE, Leung DY. A novel action of interleukin-13; induction of diminished monocyte glucocorticoïd receptor binding affinity. J Immunol 1996; 157: 2654–2659.

    PubMed  CAS  Google Scholar 

  54. Barnes PJ, Karin M. Nuclear Factor-KB. A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997; 336: 1066–1071.

    Article  PubMed  CAS  Google Scholar 

  55. Van der Burg B, Liden J, Okret S, Delaunay F, Wissink S, Van der Saag PT, et al. Nuclear factor-KB repression in anti-inflammation and immunosuppression by glucocorticoids. Trends Endocrinol Metab 1997; 8: 152–157.

    Article  PubMed  Google Scholar 

  56. Lane SJ, Arm PM, Staynov DZ, Lee TH. Chemical mutational analysis of the human glucocorticoïd receptor cDNA in glucocorticoïd-resistant bronchial asthma. Am J Respir Mol Biol 1994; 11: 42–48.

    Article  CAS  Google Scholar 

  57. Adcock IM, Lane SJ, Brown CR, Peters MJ, Lee MJ, Barnes PJ. Differences in binding of glucocorticoïd receptor to dna in steroïd-resistant asthma. J Immunol 1995; 154: 3500–3505.

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Franchimont, D.P., Chrousos, G.P. (1999). Glucocorticoid Resistance and Hypersensitivity. In: Jameson, J.L. (eds) Hormone Resistance Syndromes. Contemporary Endocrinology, vol 14. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-698-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-698-0_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5418-6

  • Online ISBN: 978-1-59259-698-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics