title: Region-specific alterations in glucocorticoid receptor expression in the postmortem brain of teenage suicide victims.
abstract: BACKGROUND
  Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls.
  
  
  METHODS
  Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects.
  
  
  RESULTS
  We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls.
  
  
  CONCLUSIONS
  These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time.
authors.affiliation: University of Illinois at Chicago, Department of Psychiatry, Chicago, IL 60612, USA. Electronic address: Gnpandey@psych.uic.edu.
authors.forename: Ghanshyam N
authors.initials: GN
authors.lastname: Pandey
authors.forename: Hooriyah S
authors.initials: HS
authors.lastname: Rizavi
authors.forename: Xinguo
authors.initials: X
authors.lastname: Ren
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Dwivedi
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
mesh_terms: D000293:Adolescent; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis; D013405:Suicide; D014157:Transcription Factors / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; C404226:TSC22D3 protein, human; D014157:Transcription Factors; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta
keywords: Amygdala; GILZ; Glucocorticoid receptors; HPA axis; Hippocampus; Mineralocorticoid receptors; Postmortem brain; Prefrontal cortex; Subiculum; Teenage suicide