The reduction in negative feedback sensitivity underlies seasonal changes in corticosterone in free-living migrant white-crowned sparrows

The CORT-Flexibility Hypothesis proposes that seasonal changes in corticosterone can fine tune the onset of breeding. Circulating corticosterone is mediated by the hypothalamic pituitary adrenal (HPA) axis in response to environmental challenges. Corticosterone is regulated by negative feedback through mineralocorticoid (MR) and glucocorticoid (GR) receptors, although glucocorticoid levels that reach the receptors are regulated by 11β-Hydroxysteroid dehydrogenase (11βHSD1) which reactivates and 11βHSD2 which deactivates the hormone. We sampled plasma corticosterone in free-living male and female migratory white-crowned sparrows (Zonotrichia leucophrys gambelli) across their annual cycle and collected tissues during breeding, pre-basic molt, and winter stages to quantify gene expression in the hippocampus, hypothalamus, pituitary, and adrenal gland. Peak corticosterone production occurred during the territoriality and egg laying stages of the annual cycle. GR and MR mRNA expression were downregulated during breeding compared to winter in the hippocampus (not MR), hypothalamus, pituitary, and adrenal gland (not GR). 11βHSD2 mRNA was higher during breeding compared to winter in all tissues except the adrenal gland, and was the only gene to differ between sexes during breeding. While 11βHSD1 mRNA was unaffected by life history stage in any tissue measured. We found no change in mRNA for cholesterol esterase, side chain cleavage enzyme, or steroid acute regulatory protein in the adrenal gland. These data suggest that the seasonal peak in corticosterone is mediated through reductions in negative feedback sensitivity at multiple levels within the HPA axis.