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.
Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Piotr
P
Chmielarz
Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Grzegorz
G
Kreiner
Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: nfnalepa@cyf-kr.edu.pl.
Irena
I
Nalepa
D059331:Adrenergic Neurons / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003345:Corticosterone / Q000097:blood*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011965:Receptors, Glucocorticoid / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012727:Sex Characteristics
D011965:Receptors, Glucocorticoid; D003345:Corticosterone
Female; Glucocorticoid receptor; Mouse; Mutation; Noradrenergic neurons