HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Whorwood, C. B. Articles by Byrne, C. D. Search for Related Content PubMed PubMed Citation Articles by Whorwood, C. B. Articles by Byrne, C. D. Social Bookmarking                What's this?

Increased Glucocorticoid Receptor Expression in Human Skeletal Muscle Cells May Contribute to the Pathogenesis of the Metabolic Syndrome

¹ Endocrine and Metabolism Unit, University Department of Medicine, University of Portsmouth, Portsmouth, U.K.
² MRC Unit, Southampton General Hospital, Southampton, U.K.

Altered glucocorticoid hormone action may contribute to the etiology of the metabolic syndrome, but the molecular mechanisms are poorly defined. Tissue sensitivity to glucocorticoid is regulated by expression of the glucocorticoid receptor (GR)- and 11ß-hydroxysteroid dehydrogenase type I (11ß-HSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed GR and 11ß-HSD1 expression in skeletal myoblasts from men (n = 14) with contrasting levels of insulin sensitivity (euglycemic clamp measurements of insulin-dependent glucose disposal rate), blood pressure, and adiposity. Positive associations were evident between myoblast expression of GR under basal conditions and levels of insulin resistance (r² = 0.34, P < 0.05), BMI (r² = 0.49, P < 0.01), percent body fat (r² = 0.34, P < 0.02), and blood pressure (r² = 0.86, P < 0.001). Similar associations were evident when myoblasts were incubated with physiological levels of cortisol (P < 0.01 for all). Importantly, GR expression was unaffected by variations in in vivo concentrations of insulin, IGF-1, or glucose concentrations. In common with the GR, 11ß-HSD1 expression in myoblasts incubated with physiological concentrations of cortisol in vitro was positively associated with levels of insulin resistance (r² = 0.68, P < 0.001), BMI (r² = 0.63, P < 0.005), and blood pressure (r² = 0.27, P < 0.05). Regulation of GR and 11ß-HSD1 by cortisol was abolished by the GR antagonist RU38486. In summary, our data suggest that raised skeletal muscle cell expression of GR and 11ß -HSD1-mediated regulation of intracellular cortisol may play a fundamental role in mechanisms contributing to the pathogenesis of the metabolic syndrome.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				Z. Yang, C. Guo, P. Zhu, W. Li, L. Myatt, and K. Sun Role of glucocorticoid receptor and CCAAT/enhancer-binding protein {alpha} in the feed-forward induction of 11{beta}-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts J. Endocrinol., November 1, 2007; 195(2): 241 - 253. [Abstract] [Full Text] [PDF]

				C. Jang, V. R. Obeyesekere, R. J. Dilley, Z. Krozowski, W. J. Inder, and F. P. Alford Altered Activity of 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2 in Skeletal Muscle Confers Metabolic Protection in Subjects with Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3314 - 3320. [Abstract] [Full Text] [PDF]

				S. Nakano, Y. Inada, H. Masuzaki, T. Tanaka, S. Yasue, T. Ishii, N. Arai, K. Ebihara, K. Hosoda, K. Maruyama, et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1213 - E1222. [Abstract] [Full Text] [PDF]

				S. E Kasim-Karakas, W. M Cunningham, and A. Tsodikov Relation of nutrients and hormones in polycystic ovary syndrome Am. J. Clinical Nutrition, March 1, 2007; 85(3): 688 - 694. [Abstract] [Full Text] [PDF]

				C. J McNeil, M. O Nwagwu, A. M Finch, K. R Page, A. Thain, H. J McArdle, and C. J Ashworth Glucocorticoid exposure and tissue gene expression of 11{beta} HSD-1, 11{beta} HSD-2, and glucocorticoid receptor in a porcine model of differential fetal growth Reproduction, March 1, 2007; 133(3): 653 - 661. [Abstract] [Full Text] [PDF]

				D. Qi and B. Rodrigues Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E654 - E667. [Abstract] [Full Text] [PDF]

				S. Kidambi, J. M. Kotchen, C. E. Grim, H. Raff, J. Mao, R. J. Singh, and T. A. Kotchen Association of Adrenal Steroids With Hypertension and the Metabolic Syndrome in Blacks Hypertension, March 1, 2007; 49(3): 704 - 711. [Abstract] [Full Text] [PDF]

				Y. Liu, C. Yan, Y. Wang, Y. Nakagawa, N. Nerio, A. Anghel, K. Lutfy, and T. C. Friedman Liver X Receptor Agonist T0901317 Inhibition of Glucocorticoid Receptor Expression in Hepatocytes May Contribute to the Amelioration of Diabetic Syndrome in db/db Mice Endocrinology, November 1, 2006; 147(11): 5061 - 5068. [Abstract] [Full Text] [PDF]

				S. Fediuc, J. E. Campbell, and M. C. Riddell Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats J Appl Physiol, June 1, 2006; 100(6): 1867 - 1875. [Abstract] [Full Text] [PDF]

				A. E. Coutinho, J. E. Campbell, S. Fediuc, and M. C. Riddell Effect of voluntary exercise on peripheral tissue glucocorticoid receptor content and the expression and activity of 11beta-HSD1 in the Syrian hamster J Appl Physiol, May 1, 2006; 100(5): 1483 - 1488. [Abstract] [Full Text] [PDF]

				A. Hermanowski-Vosatka, J. M. Balkovec, K. Cheng, H. Y. Chen, M. Hernandez, G. C. Koo, C. B. Le Grand, Z. Li, J. M. Metzger, S. S. Mundt, et al. 11{beta}-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice J. Exp. Med., August 15, 2005; 202(4): 517 - 527. [Abstract] [Full Text] [PDF]

				J. Ruzzin and J. Jensen Contraction activates glucose uptake and glycogen synthase normally in muscles from dexamethasone-treated rats Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E241 - E250. [Abstract] [Full Text] [PDF]

				E. S. Ford Risks for All-Cause Mortality, Cardiovascular Disease, and Diabetes Associated With the Metabolic Syndrome: A summary of the evidence Diabetes Care, July 1, 2005; 28(7): 1769 - 1778. [Abstract] [Full Text] [PDF]

				P. B. Jacobson, T. W. von Geldern, L. Ohman, M. Osterland, J. Wang, B. Zinker, D. Wilcox, P. T. Nguyen, A. Mika, S. Fung, et al. Hepatic Glucocorticoid Receptor Antagonism Is Sufficient to Reduce Elevated Hepatic Glucose Output and Improve Glucose Control in Animal Models of Type 2 Diabetes J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 191 - 200. [Abstract] [Full Text] [PDF]

				R. Basu, R. J. Singh, A. Basu, E. G. Chittilapilly, M. C. Johnson, G. Toffolo, C. Cobelli, and R. A. Rizza Obesity and Type 2 Diabetes Do Not Alter Splanchnic Cortisol Production in Humans J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3919 - 3926. [Abstract] [Full Text] [PDF]

				D. J. Brotman, J. P. Girod, M. J. Garcia, J. V. Patel, M. Gupta, A. Posch, S. Saunders, G. Y. H. Lip, S. Worley, and S. Reddy Effects of Short-Term Glucocorticoids on Cardiovascular Biomarkers J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3202 - 3208. [Abstract] [Full Text] [PDF]

				Y. Liu, Y. Nakagawa, Y. Wang, R. Sakurai, P. V. Tripathi, K. Lutfy, and T. C. Friedman Increased Glucocorticoid Receptor and 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Hepatocytes May Contribute to the Phenotype of Type 2 Diabetes in db/db Mice Diabetes, January 1, 2005; 54(1): 32 - 40. [Abstract] [Full Text] [PDF]

				J. R. SECKL and M. J. MEANEY Glucocorticoid Programming Ann. N.Y. Acad. Sci., December 1, 2004; 1032(1): 63 - 84. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response Endocr. Rev., October 1, 2004; 25(5): 831 - 866. [Abstract] [Full Text] [PDF]

				J. R. Seckl, N. M. Morton, K. E. Chapman, and B. R. Walker Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue Recent Prog. Horm. Res., January 1, 2004; 59(1): 359 - 393. [Abstract] [Full Text]

				D. J. Wake, E. Rask, D. E. W. Livingstone, S. Soderberg, T. Olsson, and B. R. Walker Local and Systemic Impact of Transcriptional Up-Regulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue in Human Obesity J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3983 - 3988. [Abstract] [Full Text] [PDF]

				D. Tiosano, I. Eisentein, D. Militianu, G. P. Chrousos, and Z.'e. Hochberg 11{beta}-Hydroxysteroid Dehydrogenase Activity in Hypothalamic Obesity J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 379 - 384. [Abstract] [Full Text] [PDF]

				R. C. Andrews, O. Herlihy, D. E. W. Livingstone, R. Andrew, and B. R. Walker Abnormal Cortisol Metabolism and Tissue Sensitivity to Cortisol in Patients with Glucose Intolerance J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5587 - 5593. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden American Association of Clinical Endocrinologists Meeting, May 2002 Diabetes Care, August 1, 2002; 25(8): 1464 - 1471. [Full Text] [PDF]