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Background/aim: Healthy individuals present variable responses of the hypothalamic-pituitary-adrenal (HPA) axis induced by different patterns of physical training. The aim of this study was to evaluate whether prolonged low-grade physical training influences the HPA axis and also glucocorticoid receptor-alpha (GRalpha) mRNA levels in mononuclear cells of obese adolescents., Methods: We studied 19 patients with BMI above the 95th percentile (male:female ratio 7:12) aged from 9.5 to 15.5 years. Patients underwent a 12-week physical exercise program. Before and after exercise, in vivo glucocorticoid sensitivity was determined by employing a very-low-dose intravenous dexamethasone suppression test, and in vitro GRalpha mRNA levels were evaluated by quantitative real-time PCR., Results: After exercise there was a trend to reduce the in vivo glucocorticoid sensitivity (p = 0.071) and a significant increase in GRalpha mRNA levels (p = 0.025)., Conclusion: For this subset of obese adolescents, prolonged low-grade physical training tended to reduce glucocorticoid sensitivity. The discrepancy of cortisol response to dexamethasone and the GRalpha mRNA measurement suggest a post-receptor phenomenon or should be related to target tissue-specific differences in glucocorticoid sensitivity. Future studies should address the adaptive GRalpha mRNA during different exercise protocols, and also the correlation of pituitary sensitivity with glucocorticoid target tissue sensitivity., (Copyright 2010 S. Karger AG, Basel.)