Selective ablation of glucocorticoid receptors in the noradrenergic system affects evening corticosterone levels in a sex-dependent manner

Background: The hypothalamic-pituitary-adrenal (HPA) axis, which is involved in the release of corticosterone in response to stress, exhibits large circadian variations in its activity that can also be regulated by the noradrenergic system, thereby contributing to the pathophysiology of depression. We have recently shown that mice in which glucocorticoid receptors (GR) are selectively ablated in the noradrenergic system (GR(DBHCre) mice) exhibit sex-dependent phenotype alterations, manifested as increased anxiety- and depressive-like behaviors in female but not male mutants. Methods: In this study, we investigated the regulation of circadian HPA axis activity in GR(DBHCre) transgenic mice by measuring plasma corticosterone levels. Results: We found that evening plasma corticosterone increase was profoundly higher in females than males, and this diversification was further augmented in mutant GR(DBHCre) mice. Conclusions: Our results provide evidence of the involvement of the noradrenergic system in the regulation of the sexually dimorphic circadian activity of the HPA axis. (C) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.