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Neuroendocrine Function After Hypothalamic Depletion of Glucocorticoid Receptors in Male and Female Mice.
- Source :
-
Endocrinology [Endocrinology] 2015 Aug; Vol. 156 (8), pp. 2843-53. Date of Electronic Publication: 2015 Jun 05. - Publication Year :
- 2015
-
Abstract
- Glucocorticoids act rapidly at the paraventricular nucleus (PVN) to inhibit stress-excitatory neurons and limit excessive glucocorticoid secretion. The signaling mechanism underlying rapid feedback inhibition remains to be determined. The present study was designed to test the hypothesis that the canonical glucocorticoid receptors (GRs) is required for appropriate hypothalamic-pituitary-adrenal (HPA) axis regulation. Local PVN GR knockdown (KD) was achieved by breeding homozygous floxed GR mice with Sim1-cre recombinase transgenic mice. This genetic approach created mice with a KD of GR primarily confined to hypothalamic cell groups, including the PVN, sparing GR expression in other HPA axis limbic regulatory regions, and the pituitary. There were no differences in circadian nadir and peak corticosterone concentrations between male PVN GR KD mice and male littermate controls. However, reduction of PVN GR increased ACTH and corticosterone responses to acute, but not chronic stress, indicating that PVN GR is critical for limiting neuroendocrine responses to acute stress in males. Loss of PVN GR induced an opposite neuroendocrine phenotype in females, characterized by increased circadian nadir corticosterone levels and suppressed ACTH responses to acute restraint stress, without a concomitant change in corticosterone responses under acute or chronic stress conditions. PVN GR deletion had no effect on depression-like behavior in either sex in the forced swim test. Overall, these findings reveal pronounced sex differences in the PVN GR dependence of acute stress feedback regulation of HPA axis function. In addition, these data further indicate that glucocorticoid control of HPA axis responses after chronic stress operates via a PVN-independent mechanism.
- Subjects :
- Animals
Circadian Rhythm genetics
Feedback, Physiological
Female
Gene Knockdown Techniques
Hypothalamo-Hypophyseal System physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pituitary-Adrenal System physiology
Receptors, Glucocorticoid metabolism
Stress, Psychological genetics
Stress, Psychological metabolism
Gene Deletion
Hypothalamus metabolism
Neurosecretory Systems physiology
Receptors, Glucocorticoid genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 156
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 26046806
- Full Text :
- https://doi.org/10.1210/en.2015-1276