Tissue-specific adaptive levels of glucocorticoid receptor alpha mRNA and their relationship with insulin resistance
Genetics and Molecular Research
Insulin resistance is an underlying cause of metabolic changes associated with cardiovascular diseases. Glucocorticoids are known determinant factors of insulin resistance. We quantified glucocorticoid receptor alpha (GRα) mRNA and 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mRNA in various tissues of 35 patients with previously established cardiovascular disease. This was a prospective study in a cardiac surgery patient setting. Samples of subcutaneous adipose tissue, epicardial
... sue, epicardial fat, muscle, and peripheral blood mononuclear cells were examined. GRα and 11β-HSD1 mRNA were determined by real-time PCR. Mean age was 54.4 years. A significantly higher level of GRα mRNA was observed in muscle, with mean = 43.6 arbitrary units, median (p25-p75) = 39.4, compared to epicardial adipose tissue, with mean = 34.2, median (p25-p75) = 27.6, and to subcutaneous adipose tissue, with mean = 29.0, median (p25-p75) = 19.0, and lymphocytes, with mean = 17.5, median (p25-p75) = 14.02. When patients with diabetes mellitus were compared to patients ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 3975-3987 (2012) R.B. Castro et al. without insulin resistance, significantly lower levels of GRα mRNA were observed in epicardial fat. Lymphocytes had the lowest 11β-HSD1 mRNA concentration. We also observed significantly reduced 11β-HSD1 mRNA levels in visceral fat when compared with muscle tissue. GRα and 11β-HSD1 mRNA levels differed among tissues involved in the pathophysiology of metabolic syndrome. We conclude that epicardial adipose tissue has lower GRα mRNA levels in insulin-resistant patients; this seems to be an adaptive and protective mechanism.