PMID- 26046806
OWN - NLM
STAT- MEDLINE
DCOM- 20151006
LR  - 20210312
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 156
IP  - 8
DP  - 2015 Aug
TI  - Neuroendocrine Function After Hypothalamic Depletion of Glucocorticoid Receptors 
      in Male and Female Mice.
PG  - 2843-53
LID - 10.1210/en.2015-1276 [doi]
AB  - 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.
FAU - Solomon, Matia B
AU  - Solomon MB
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Loftspring, Matthew
AU  - Loftspring M
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - de Kloet, Annette D
AU  - de Kloet AD
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Ghosal, Sriparna
AU  - Ghosal S
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Jankord, Ryan
AU  - Jankord R
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Flak, Jonathan N
AU  - Flak JN
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Wulsin, Aynara C
AU  - Wulsin AC
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Krause, Eric G
AU  - Krause EG
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Zhang, Rong
AU  - Zhang R
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Rice, Taylor
AU  - Rice T
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - McKlveen, Jessica
AU  - McKlveen J
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Myers, Brent
AU  - Myers B
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Tasker, Jeffrey G
AU  - Tasker JG
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
FAU - Herman, James P
AU  - Herman JP
AD  - Department of Psychiatry and Behavioral Neuroscience (M.B.S., M.L., A.D.d.K., 
      S.G., R.J., J.N.F., A.C.W., E.G.K., R.Z., T.R., J.M., B.M., J.P.H.), College of 
      Medicine, University of Cincinnati, Cincinnati, Ohio 45237-1625; Department of 
      Psychology (M.B.S.), University of Cincinnati, Cincinnati, Ohio 45237-1625; and 
      Department of Cell and Molecular Biology (J.G.T.), Tulane University, New 
      Orleans, Louisiana 70118-5698.
LA  - eng
GR  - MH069725/MH/NIMH NIH HHS/United States
GR  - MH066958/MH/NIMH NIH HHS/United States
GR  - R01 MH066958/MH/NIMH NIH HHS/United States
GR  - K12 HD051953/HD/NICHD NIH HHS/United States
GR  - R01 MH069860/MH/NIMH NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - MH049698/MH/NIMH NIH HHS/United States
GR  - T32 DK094775/DK/NIDDK NIH HHS/United States
GR  - R01 MH069725/MH/NIMH NIH HHS/United States
GR  - K12HD051953/HD/NICHD NIH HHS/United States
GR  - R01 MH049698/MH/NIMH NIH HHS/United States
GR  - F30 NS095578/NS/NINDS NIH HHS/United States
GR  - MH069860/MH/NIMH NIH HHS/United States
GR  - T32 GM063483/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150605
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Receptors, Glucocorticoid)
SB  - IM
CIN - Endocrinology. 2015 Aug;156(8):2747-8. PMID: 26186157
MH  - Animals
MH  - Circadian Rhythm/genetics
MH  - Feedback, Physiological
MH  - Female
MH  - *Gene Deletion
MH  - Gene Knockdown Techniques
MH  - Hypothalamo-Hypophyseal System/physiology
MH  - Hypothalamus/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurosecretory Systems/*physiology
MH  - Pituitary-Adrenal System/physiology
MH  - Receptors, Glucocorticoid/*genetics/metabolism
MH  - Stress, Psychological/genetics/metabolism
PMC - PMC4511133
EDAT- 2015/06/06 06:00
MHDA- 2015/10/07 06:00
PMCR- 2016/08/01
CRDT- 2015/06/06 06:00
PHST- 2015/06/06 06:00 [entrez]
PHST- 2015/06/06 06:00 [pubmed]
PHST- 2015/10/07 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - 10.1210/en.2015-1276 [pii]
AID - EN-15-1276 [pii]
AID - 10.1210/en.2015-1276 [doi]
PST - ppublish
SO  - Endocrinology. 2015 Aug;156(8):2843-53. doi: 10.1210/en.2015-1276. Epub 2015 Jun 
      5.