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Relationship between glucocorticoid receptor and response to glucocorticoid therapy in ulcerative colitis

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Diseases of the Colon & Rectum

Abstract

PURPOSE: To clarify the relationship between the glucocorticoid receptor and the effectiveness of glucocorticoid therapy in patients with ulcerative colitis, we investigated the number and apparent dissociation constant of glucocorticoid receptor in peripheral blood mononuclear leukocytes of patients with ulcerative colitis. MATERIALS AND METHODS: Eleven patients with ulcerative colitis (5 who responded to intravenous glucocorticoids and 6 who did not) and ten control subjects were studied. The number and apparent dissociation constant of glucocorticoid receptor were measured using a whole-cell binding assay. Results were expressed as a median (interquartile range). RESULTS: The number of glucocorticoid receptors from the six nonresponders, five responders, and ten healthy controls were 4922 (range, 4484–5643), 3413 (range, 3183–4450), and 3610 (range, 2594–3979) binding sites/cell, respectively. The apparent dissociation constant of the glucocorticoid receptors from the nonresponders, responders, and healthy controls were 7.03 (range, 5.66–10), 4.27 (range, 4–5.13), and 6.18 (range, 5.86–6.74) nM, respectively. Nonresponders had a significant increase both in the number of binding sites and in the apparent dissociation constant compared with responders (P=0.045;P=0.029). CONCLUSIONS: The increased number and apparent dissociation constant of glucocorticoid receptor are closely associated with the effectiveness of glucocorticoid therapy. The measurement of the number and apparent dissociation constant of glucocorticoid receptor may be useful in predicting response to glucocorticoids.

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References

  1. Truelove SC, Jewell DP. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet 1974;1:1067–70.

    PubMed  Google Scholar 

  2. Catelli MG, Binart N, Jung-Testas I,et al. The common 90-kDa protein component of non-transformed ‘8s’ steroid receptors is a heat shock protein. EMBO J 1985;4:3131–5.

    PubMed  Google Scholar 

  3. Schuh S, Yonemoto W, Brugge J,et al. A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus t ransforming protein, pp60v-src. J Biol Chem 1985;260:14292–4

    PubMed  Google Scholar 

  4. Sanchez ER, Toft DO, Schlesinger MJ, Pratt WB. Evidence that the 90- kDa phosphoprotein associated with the untransformed L-cell glucocorticoid receptor is a murine heat shock protein. J Biol Chem 1985;260:12398–401.

    PubMed  Google Scholar 

  5. Guyre PM, Girard MT, Morganelli PM, Manganiello PD. Glucocorticoid effects on the production and actions of immune cytokines. J Steroid Biochem 1988;30:89–93.

    PubMed  Google Scholar 

  6. Kern JA, Lamb RJ, Reed JL, Daniele RP, Nowell PC. Dexamethasone inhibition of interleukin beta production by human monocytes: Posttranscriptional mechanisms. J Clin Invest 1988;81:237–44.

    PubMed  Google Scholar 

  7. Jonat C, Rahmsdorf HJ, Park KK,et al. Antitumor promotion and antiinflammation: down-modulation of AP-1 (fos/Jun) activity by glucocorticoid hormone. Cell 1990;62:1189–204.

    PubMed  Google Scholar 

  8. Yang-Yan HF, Chamberd JC, Sun YL,et al. Transcriptional interference between c-jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell 1990;62:1205–15.

    PubMed  Google Scholar 

  9. Schule R, Rangarajan P, Kleiwer S,et al. Functional antagonism between oncoprotein c-jun and the glucocorticoid receptor. Cell 1990;62;1217–26.

    PubMed  Google Scholar 

  10. Lippmann ME, Yarbro GK, Leventhal BG. Clinical implications of glucocorticoid receptors in human leukemia. Cancer Res 1978;38:4251–6.

    PubMed  Google Scholar 

  11. Sher ER, Leung DY, Surs W,et al. Steroid-resistant asthma: cellular mechanisms contributing to inadequate response to glucocorticoid therapy. J Clin Invest 1994;93:33–9.

    PubMed  Google Scholar 

  12. Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on a therapeutic trial. BMJ 1955;2:1041–8.

    Google Scholar 

  13. Murakami T, Brandon D, Rodbard D, Loriaux DL, Lipsett MB. Glucocorticoid receptor in circulating mononuclear leukocytes. Endocrinology 1979;104:500–5.

    PubMed  Google Scholar 

  14. Scatchard G. The attractions of proteins for small molecules and ions. Ann N Y Acad Sci 1949;51:660–72.

    Google Scholar 

  15. Alvarez J, Surs W, Leung DY, Ikle D, Gelfand EW, Szefler SJ. Steroid-resistant asthma: immunologic and pharmacologic features. J Allergy Clin Immunol 1992;89:714–21.

    PubMed  Google Scholar 

  16. Lamerts SW, Koper JW, Biemond P, den Holder FH, de Jong FH. Familial and iatrogenic cortisol receptor resistance. Cancer Res 1989;49(Suppl):2217–9.

    Google Scholar 

  17. Iida S, Gomi M, Moriwaki K,et al. Primary cortisol resistance accompanied by a reduction in glucocorticoid receptors in two members of the same family. J Clin Endocrinol Metab 1985;60:967–71.

    PubMed  Google Scholar 

  18. Nawata H, Sekiya K, Higuchi K, Kato K, Ibayashi H. Decreased deoxyribonucleic acid binding of glucocorticoid-receptor complex in cultured skin fibroblasts from a patient with the glucocorticoid resistance syndrome. J Clin Endocrinol Metab 1987;65:219–26.

    PubMed  Google Scholar 

  19. Brandon DD, Markwick AJ, Chrousos GP, Loriaux DL. Glucocorticoid resistance in humans and nonhuman primates. Cancer Res 1989;49(Suppl):2203–13.

    Google Scholar 

  20. Bronnegard M, Werner S, Gustaffuson JA. Primary cortisol resistance associated with a thermolabile glucocorticoid receptor in a patient with fatigue as the only symptom. J Clin Invest 1986;78:1270–8.

    PubMed  Google Scholar 

  21. Hurley DM, Accili D, Stratakis CA,et al. Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest 1991;87:680–6.

    PubMed  Google Scholar 

  22. Okret S, Poellinger L, Dong Y, Gustafsson J-A. Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone. Proc Natl Acad Sci U S A 1986;83:5899–903.

    PubMed  Google Scholar 

  23. McDonald AR, Maddux BA, Okabayashi Y,et al. Regulation of insulin-receptor mRNA levels by glucocorticoids. Diabetes 1987;36:779–81.

    PubMed  Google Scholar 

  24. Kristensen M, Koudahl G, Fischerman K, Jarnum S. High dose prednisone treatment in severe ulcerative colitis. Scand J Gastroenterol 1974;9:177–83.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Third Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-77, Sendai, Japan

    Takenobu Shimada M.D.,  Nobuo Hiwatashi M.D., Hideo Yamazaki M.D., Yoshitaka Kinouchi M.D. & Takayoshi Toyota M.D.

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  1. Takenobu Shimada M.D.
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  2. Nobuo Hiwatashi M.D.
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  3. Hideo Yamazaki M.D.
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  4. Yoshitaka Kinouchi M.D.
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  5. Takayoshi Toyota M.D.
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Supported in part by a grant-in-aid from the Ministry of Education, Science, and Culture of Japan.

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Shimada, T., Hiwatashi, N., Yamazaki, H. et al. Relationship between glucocorticoid receptor and response to glucocorticoid therapy in ulcerative colitis. Dis Colon Rectum 40 (Suppl 10), S54–S58 (1997). https://doi.org/10.1007/BF02062021

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