Abstract:

PURPOSE: Cortisol responses to stressful exercise are frequently investigated when studying overtraining. However, results are equivocal concerning the role cortisol contributes to maladaptation during overtraining. The intracellular steroid receptor for cortisol is the glucocorticoid receptor (GR). Recent evidence suggests the GR can be phosphorylated at several serine residues (ser134, ser211, and ser226) by the mitogen-activated protein kinase (MAPK) signaling pathway and modulates receptor function independent of hormones.  We have previously reported differences in the resting activity of MAPK after overtraining, but the phosphorylated GR (pGR) responses to overtraining have not been studied. Therefore, the purpose of this study was to determine if resting and exercise induced GR phosphorylation was augmented by a high-frequency resistance exercise overtraining stimulus.  METHODS:  Sixteen men were matched on barbell squat 1 repetition maximum (1RM) strength and randomized into a group that performed normal training or stressful training with insufficient recovery. The control group (CON; n=8, age=20.7±1.2yrs, hgt=180±10cm, body mass=83.9±10.7kg) performed three speed-squat training sessions on non-consecutive days, while the overtraining group (OT; n=8, age=21.3±2.3yrs, hgt=155±62cm, body mass=77.8±11.3kg) performed 15 training sessions over 7.5 days. Prior to (T1), and after the training intervention (T2) both groups performed and acute resistance exercise bout of 5 sets of 5 repetitions at 60% 1RM, and 3 sets of 10 repetition knee extensions. Resting and post-exercise skeletal muscle biopsies were obtained at T1 and T2. Samples were analyzed for total GR and pGR at ser134, ser211, and ser226. Serum samples were obtained at rest, after the final set of barbell squats, and 5 minutes post exercise to determine circulating cortisol concentrations. Significance determined at p < 0.05. RESULTS: The OT group had elevated cortisol values during the squat protocol at T1, but there was no cortisol response at T2. The CON group did not display an exercise induced cortisol response at any time-point (p >0.05).  pGRser134 decreased at T2 for CON (p=0.008) but was unchanged at any time point in the OT group.  pGRser226 increased at post-exercise in both groups at T1(p=0.008) and T2 (p=0.008). However, in the OT group, pGRser226 at rest was higher at T2 compared to T1 (p=0.008). The post exercise response in pGRser226 at T2 was less than the post-exercise response at T1 in OT (p=0.016). CONCLUSIONS: Despite differences in cortisol responses between groups before training, at the local skeletal muscle level pGR was similar between groups. After a period of overtraining, ser226 on the GR which regulates nuclear import and export appeared to be most influenced by the overtraining stimulus.  PRACTICAL APPLICATIONS: Coaches, athletes, and clinicians should be aware that changes in circulating cortisol following a training stimulus may not be completely reflective of changes occurring at the local skeletal muscle level. While monitoring circulating cortisol may provide valuable information about training load and stress, it is likely the GR integrates hormonal, contractile, metabolic stresses in tandem to modulate skeletal muscle adaptations during stressful training.