PMID- 19406955
OWN - NLM
STAT- MEDLINE
DCOM- 20090722
LR  - 20211203
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 202
IP  - 1
DP  - 2009 Jul
TI  - Acute or chronic stress induce cell compartment-specific phosphorylation of 
      glucocorticoid receptor and alter its transcriptional activity in Wistar rat 
      brain.
PG  - 87-97
LID - 10.1677/JOE-08-0509 [doi]
AB  - Chronic stress and impaired glucocorticoid receptor (GR) feedback are important 
      factors for the compromised hypothalamic-pituitary-adrenal (HPA) axis activity. 
      We investigated the effects of chronic 21 day isolation of Wistar rats on the 
      extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal 
      cortex (PFC). In addition to serum corticosterone (CORT), we followed GR 
      subcellular localization, GR phosphorylation at serine 232 and serine 246, 
      expression of GR regulated genes: GR, CRF and brain-derived neurotropic factor 
      (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that 
      phosphorylate GR. These parameters were also determined in animals subjected to 
      acute 30 min immobilization, which was taken as 'normal' adaptive response to 
      stress. In isolated animals, we found decreased CORT, whereas in animals exposed 
      to acute immobilization, CORT was markedly increased. Even though the GR was 
      predominantly localized in the nucleus of HIPPO and PFC in acute, but not in 
      chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated 
      under both acute and chronic stresses. Thus, the transcriptional activity of GR 
      under chronic isolation did not seem to be exclusively dependent on high serum 
      CORT levels nor on the subcellular location of the GR protein. Rather, it 
      resulted from the increased Cdk5 activation and phosphorylation of the nuclear GR 
      at serine 232 and the decreased JNK activity reflected in decreased 
      phosphorylation of the nuclear GR at serine 246. Our study suggests that this 
      nuclear isoform of hippocampal and cortical GR may be related to hypocorticism 
      i.e. HPA axis hypoactivity under chronic isolation stress.
FAU - Adzic, Miroslav
AU  - Adzic M
AD  - Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear 
      Sciences, Belgrade, Serbia.
FAU - Djordjevic, Jelena
AU  - Djordjevic J
FAU - Djordjevic, Ana
AU  - Djordjevic A
FAU - Niciforovic, Ana
AU  - Niciforovic A
FAU - Demonacos, Constantinos
AU  - Demonacos C
FAU - Radojcic, Marija
AU  - Radojcic M
FAU - Krstic-Demonacos, Marija
AU  - Krstic-Demonacos M
LA  - eng
GR  - 069024/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090430
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Receptors, Glucocorticoid)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - Cell Compartmentation/physiology
MH  - Hydrocortisone/blood
MH  - Hypothalamo-Hypophyseal System/metabolism
MH  - Male
MH  - Phosphorylation
MH  - Pituitary-Adrenal System/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein Transport
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Glucocorticoid/*metabolism/*physiology
MH  - Serine/metabolism
MH  - Stress, Physiological/*physiology
MH  - Time Factors
MH  - Tissue Distribution
MH  - *Transcriptional Activation/physiology
PMC - PMC2695659
EDAT- 2009/05/02 09:00
MHDA- 2009/07/23 09:00
PMCR- 2009/07/01
CRDT- 2009/05/02 09:00
PHST- 2009/05/02 09:00 [entrez]
PHST- 2009/05/02 09:00 [pubmed]
PHST- 2009/07/23 09:00 [medline]
PHST- 2009/07/01 00:00 [pmc-release]
AID - JOE-08-0509 [pii]
AID - JOE080509 [pii]
AID - 10.1677/JOE-08-0509 [doi]
PST - ppublish
SO  - J Endocrinol. 2009 Jul;202(1):87-97. doi: 10.1677/JOE-08-0509. Epub 2009 Apr 30.