Glucocorticoid receptor activation is associated with increased resistance to heat-induced hyperthermia and injury

Aim: Anti-inflammatory mediators likely play a key role in maintaining thermal homeostasis and providing protection against heat stress. The aim of this study was to investigate the association between activation of the glucocorticoid receptor (GR) and resistance to heat-induced hyperthermia and injury. Methods: Effects of heat exposure on core body temperature, muscle GR phosphorylation status and subcellular expression were examined in control mice and thermal acclimation (TA)-exposed mice. In addition, effects of TA and corticosterone on C2C12 mouse myoblast viability and subcellular GR were assessed during heat exposure. Results: Phosphorylated, nuclear and mitochondrial GR levels were significantly higher in the gastrocnemius muscles of mice with mild hyperthermia (tolerant), compared to mice with severe hyperthermia (intolerant) during a heat exposure test. Similar changes were found in mice after TA, compared to non-TA-exposed controls. Additional groups of TA and non-TA-exposed mice underwent a heat exposure test. TA mice presented a significantly lower hyperthermic response during heat exposure than non-TA-exposed control. C2C12 cells exposed to TA incubation had higher viability against heat shock and showed higher GR levels in their mitochondria and nuclei detected by Western blot analysis and fluorescence microscopy, compared to cells exposed to normal incubation. Furthermore, pre-incubation with 0.1 μM corticosterone increased C2C12 cell viability during heat exposure and mitochondrial and nuclear GR expression. Conclusion: The results of these in vivo and in vitro studies suggest that GR activation is associated with increased resistance against heat-induced hyperthermia and injury.