Skip to main content
SpringerLink
Log in

The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing’s syndrome (Cushing’s disease) and 10 healthy controls. Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855±1389 sites/cell which was significantly lower (p<0.05) than controls (6234±1568 sites/cell), although no significant difference was found in the mean serum cortisol level. Their mean Kd (affinity) was also significantly lower than that found in the healthy controls (obese Kd:2.92±0.84nmol/I, control Kd: 4.55±0.67nM, p<0.05). On the other hand, the receptor characteristics in Cushing’s disease patients were within the normal range. At the same time, 3-O-MG transport was determined in the same subjects. In Cushing’s disease, 3-O-MG transport was within the normal range, whereas in abdominal obesity this value was significantly lower than the healthy controls (abdominal obese: 31.90±8.20; control: 46.26±12.91 fmol/106cell. min, p<0.05). We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects (r=0.89, p<0.001), however we did not find such a correlation in Cushing’s disease (r=0.60, p>0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Proietto J., Thorburn A.W. Animal models of obesity-theories of aetiology. Baillieres Clin. Endocrinol. 8: 509, 1994.

    Article  CAS  Google Scholar 

  2. Salans L.B. The obesities. In: Felig P., Baxter J.D., Broadus A.E., Frohman L.A. (Eds.), Endocrinology and Metabolism. McGraw-Hill Book Company, New York, 1981, p. 891.

    Google Scholar 

  3. Kopelman P.G. Hormones and obesity. Baillieres Clin. Endocrinol. 8: 549, 1994.

    Article  CAS  Google Scholar 

  4. Tyrrell J.B., Forsham P.H. Glucocorticoid & adrenal androgens. In: Greenspan F.S., Forsham P.H. (Eds.), Basic & Clinical Endocrinology. Lange Medical Publications, Los Altos, California, 1984, p. 258.

    Google Scholar 

  5. Howlett T.A., Rees L.H., Besser G.M. Cushing’s syndrome. Clin. Endocrinol. Metab. 14: 911, 1985.

    Article  PubMed  CAS  Google Scholar 

  6. Von Werder K., Müller O.A. Cushing’s syndrome. In: Grossman A. (Ed.), Clinical Endocrinology. Blackwell Scientific Publications, Oxford, 1992, p. 442.

    Google Scholar 

  7. Tappy L., Randin D., Vollenweider P., Vollenweider L., Paquot N., Scherrer U., Schneiter P., Nicod P., Jequier E. Mechanisms of dexamethasone-induced insulin resistance in healthy humans. J. Clin. Endocrinol. Metab. 79: 1063, 1994.

    PubMed  CAS  Google Scholar 

  8. Tanaka H., Akama H., Ichikawa Y., Homma M., Makino I. Glucocorticoid receptor and inhibition of 3-O-methyl-D-glucose uptake by glucocorticoids in peripheral blood leukocytes from normal humans: correlation between receptor level and hormone effect in vitro. Acta Endocrinol. (Copenh.) 126: 29, 1992.

    CAS  Google Scholar 

  9. Gurwitz J.H., Bohn R.L., Glynn R.J., Monane M., Mogun H., Avorn J. Glucocorticoids and the risk for initiation of hypoglycemic therapy. Arch. Intern. Med. 154: 97, 1994.

    Article  PubMed  CAS  Google Scholar 

  10. Bray G. Fat distribution and body weight. Ob. Res. 1: 203, 1993.

    Article  CAS  Google Scholar 

  11. Tanaka H., Akama H., Ichikawa Y., Homma M., Oshima H. Glucocorticoid receptors in normal leukocytes: effects of age, gender, season and plasma cortisol concentrations. Clin. Chem. 37: 1715, 1991.

    PubMed  CAS  Google Scholar 

  12. Damm P., Binder C. Glucocorticoid receptors in monocytes in type 1 diabetes mellitus. Clin. Chim. Acta 184: 167, 1989.

    Article  PubMed  CAS  Google Scholar 

  13. Scatchard G. The attractions of proteins by small molecules and ions. Ann. N.Y. Acad. Sci. 51: 660, 1949.

    Article  CAS  Google Scholar 

  14. Brentani M.M., Wajchenberg B.L., Cesar F.P., Martins V.R. Regulation of the glucocorticoid receptor by glucocorticoids in human mononuclear leukocytes. Horm. Res. 24: 9, 1986.

    Article  PubMed  CAS  Google Scholar 

  15. Pardes E., De Yampey J.E., Moses D.F., De Nicola A.F. Regulation of glucocorticoid receptors in human mononuclear cells: Effects of glucocorticoid treatment, Cushing’s disease and ketoconazole. J. Steroid Biochem. 39: 233, 1991.

    Article  CAS  Google Scholar 

  16. Girardin E., Garoscio-Cholet M., Dechaud H., Lejeune H., Carrier E., Tourniaire J., Pugeat M. Glucocorticoid receptors in lymphocytes in anorexia nervosa. Clin. Endocrinol. (Oxf.) 35: 79, 1991.

    Article  CAS  Google Scholar 

  17. Kontula K., Pelkonen R., Andersson L., Sivula A. Glucocorticoid receptors in adrenocorticoid disorders. J. Clin. Endocrinol. Metab. 51: 654, 1980.

    Article  PubMed  CAS  Google Scholar 

  18. Schlechte J.A., Sherman B.M. Decreased glucocorticoid receptor binding in adrenal insufficiency. J. Clin. Endocrinol. Metab. 54: 145, 1982.

    Article  PubMed  CAS  Google Scholar 

  19. Haber R.S., Weinstein S.P. Role of glucose transporters in glucocorticoid-induced insulin resistance: GLUT 4 isoform in rat skeletal muscle is not decreased by dexamethasone. Diabetes 41: 728, 1992.

    Article  PubMed  CAS  Google Scholar 

  20. Yanovski J.A., Culter G.B. Glucocorticoid action and clinical features of Cushing’s syndrome. Endocrinol. Metab. Clin. North Am. 23: 487, 1994.

    PubMed  CAS  Google Scholar 

  21. Weaver J.U., Hitman G.A., Kopelman P.G. An association between a Bcll restriction fragment length polymorphism of glucocorticoid receptor locus and hyperinsulinemia in obese women. J. Mol. Endocrinol. 9: 295, 1992.

    Article  PubMed  CAS  Google Scholar 

  22. Slavnov V.N., Epshtein E.V. Somatotrophic, thyrotrophic and adrenotrophic functions of the anterior pituitary in obesity. Endocrinologie 19: 213, 1977.

    Google Scholar 

  23. Tsai H.J., Romsos D.R. Glucocorticoid and mineralocorticoid receptor-binding characteristics in obese (ob/ob) mice. Am. J. Physiol. 261: 499, 1991.

    Google Scholar 

  24. Webb M.L., Flynn J.J., Schmidt T.J., Margules D.L., Litwack G. Decreased glucocorticoid binding and receptor activation in brain of genetically diabetic (mdb/mdb) mice. J. Steroid Biochem. 25: 649, 1986.

    Article  PubMed  CAS  Google Scholar 

  25. Shargill N.S., Al-Baker I., York D.A. Normal levels of serum corticosterone and hepatic glucocorticoid receptors in obese (fa/fa) rats. Biosci. Rep. 7: 843, 1987.

    Article  PubMed  CAS  Google Scholar 

  26. Svec F. Glucocorticoid receptor regulation. Life Sci. 36: 2359, 1985.

    Article  PubMed  CAS  Google Scholar 

  27. Bodwell J.E., Hu L.M., Munck A. Glucocorticoid receptors; ATP-dependent cycling and hormone-dependent hyperphosphorilation. J. Steroid Biochem. 47: 31, 1993.

    Article  CAS  Google Scholar 

  28. Wheeler R.H., Leach K.L., La Forest A.C., O’Toole T.E., Pratt W.B. Glucocorticoid receptor activation and inactivation in cultured human lymphocytes. J. Biol. Chem. 256: 434, 1981.

    PubMed  CAS  Google Scholar 

  29. Amatruda J.M., Livingston J.N., Lockwood D.H. Cellular mechanisms in selected states of insulin resistance: human obesity, glucocorticoid excess and chronic renal failure. Diabetes Metab. Rev. 1: 293, 1985.

    Article  PubMed  CAS  Google Scholar 

  30. Cooney G.J., Storlien L.H. Insulin action, thermogenesis and obesity. Baillieres Clin. Endocrinol. Metab. 8: 481, 1994.

    Article  PubMed  CAS  Google Scholar 

  31. Ramsey T.G. Fat cells. Endoc. Metab. Clin. 25: 847, 1996.

    Article  Google Scholar 

  32. Daneman D., Zinman B., Elliott M.E., Bilan P.J., Klip A. Insulin-stimulated glucose transport in circulating mononuclear cells from nondiabetic and IDDM subjects. Diabetes 41: 227, 1992.

    Article  PubMed  CAS  Google Scholar 

  33. Garvey W.T., Birnbaum M.J. Cellular action and insulin resistance. Baillieres Clin. Endocrinol. Metab. 7: 785, 1993.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Biology, Istanbul University, Istanbul, Turkey

    M. Güven, T. Ulutin &  Gönül Kanigür-Sultuybek

  2. Department of Internal Medicine, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey

    H. Hatemi, E. Taşan, Y. Altuntaş & V. Tezcan

Authors
  1. M. Güven
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Hatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Taşan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Altuntaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Ulutin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Tezcan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gönül Kanigür-Sultuybek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Güven, M., Hatemi, H., Taşan, E. et al. The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity. J Endocrinol Invest 21, 656–661 (1998). https://doi.org/10.1007/BF03350794

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03350794

Key-words

Search

Navigation