Intracellular negative feedback mechanisms in blubber and muscle moderate acute stress responses in fasting seals.

Animals may limit the cost of stress responses during key life history stages such as breeding and molting by reducing tissue sensitivity to energy-mobilizing stress hormones (e.g. cortisol). We measured expression of genes encoding glucocorticoid receptor (GR, NR3C1), GR inhibitor (FKBP5) and cortisol-inactivating enzyme (HSD11B2) in blubber and muscle of northern elephant seals before and after stress axis stimulation by adrenocorticotropic hormone (ACTH) early and late in a fasting period associated with molting. ACTH elevated cortisol levels for >24 h and increased FKBP5 and HSD11B2 expression while downregulating NR3C1 expression in blubber and muscle, suggesting robust intracellular negative feedback in peripheral tissues. This feedback was maintained over prolonged fasting, despite differences in baseline cortisol and gene expression levels between early and late molt, suggesting that fasting-adapted animals use multiple tissue-specific, intracellular negative feedback mechanisms to modulate downstream impacts of acute stress responses during key life history stages.

Adrenal response to ACTH challenge alters thyroid and immune function and varies with body reserves in molting adult female northern elephant seals.

Intrinsic stressors associated with life-history stages may alter the responsiveness of the hypothalamic-pituitary-adrenal axis and responses to extrinsic stressors. We administered adrenocorticotropic hormone (ACTH) to 24 free-ranging adult female northern elephant seals (NESs) at two life-history stages: early and late in their molting period and measured a suite of endocrine, immune, and metabolite responses. Our objective was to evaluate the impact of extended, high-energy fasting on adrenal responsiveness. Animals were blood sampled every 30 min for 120 min post-ACTH injection, then blood was sampled 24 h later. In response to ACTH injection, cortisol levels increased 8- to 10-fold and remained highly elevated compared with baseline at 24 h. Aldosterone levels increased 6- to 9-fold before returning to baseline at 24 h. The magnitude of cortisol and aldosterone release were strongly associated, and both were greater after extended fasting. We observed an inverse relationship between fat mass and the magnitude of cortisol and aldosterone responses, suggesting that body reserves influenced adrenal responsiveness. Sustained elevation in cortisol was associated with alterations in thyroid hormones; both tT3 and tT4 concentrations were suppressed at 24 h, while rT3 increased. Immune cytokine IL-1ß was also suppressed after 24 h of cortisol elevation, and numerous acute and sustained impacts on substrate metabolism were evident. Our data suggest that female NESs are more sensitive to stress after the molt fast and that acute stress events can have important impacts on metabolism and immune function. These findings highlight the importance of considering life-history context when assessing the impacts of anthropogenic stressors on wildlife.