Seasonal changes in acute stressor-mediated plasma glucocorticoid regulation in New World flying squirrels

Southern flying squirrels have higher circulating cortisol levels than most vertebrates. However, regulation of tissue exposure to cortisol by the hormone's carrier protein, corticosteroid-binding globulin (CBG), appears to be altered due to lower-than-expected CBG expression levels, and a reduced affinity for cortisol. To assess the capacity of flying squirrels to regulate acute stress-mediated cortisol levels, we used the dexamethasone (DEX) suppression test followed by the adrenocorticotropic hormone (ACTH) stimulation test in both the breeding and non-breeding seasons, and quantified resultant changes in plasma cortisol and relative CBG levels. Regulation of cortisol via negative feedback, and the acute stress response appeared to function as they do in other vertebrates during the breeding season, but response to DEX in the non-breeding season showed that the sensitivity of the negative feedback mechanism changed across seasons. The relatively high concentrations of DEX required to induce negative feedback suggests that southern flying squirrels have a reduced sensitivity to cortisol compared with other vertebrates, and that high circulating cortisol levels may be required to compensate for low target tissue responsiveness in this species. Cortisol, but not CBG levels, were higher during the non-breeding than breeding season, and females had higher cortisol and CBG levels than males. Our data suggest that flying squirrel cortisol levels are regulated by negative feedback at a higher set point than in related species. Seasonal changes in cortisol levels, target tissue sensitivity to DEX, and in the capacity to respond to stressors appear to be part of the underlying physiology of southern flying squirrels, and may be required to maximize fitness in the face of tradeoffs between survival and reproduction.