title: Phosphorylation of leukocyte glucocorticoid receptor in patients with current episode of major depressive disorder.
abstract: The impaired glucocorticoid receptor (GR) signaling has long been considered one of the cornerstones in understanding the pathophysiology of depression. Since the phosphorylation of GR is very important for GR function, in this study we investigated whether GR phosphorylation at serine 211 (pGR-S211) and serine 226 (pGR-S226) is altered in patients with current episode of major depressive disorder (MDD). Particularly, in 30 MDD patients and 35 controls we assessed the levels of nuclear total GR (tGR), pGR-S211 and pGR-S226 in peripheral blood mononuclear cells (PBMC) using Western blot technique, along with plasma cortisol concentrations from the same blood samples. Our results demonstrated increased phosphorylation of GR at S226 (p<0.001) and, to a less extent, at S211 (p<0.05) in MDD patients compared to controls. Consequently, the pGR-S211/pGR-S226 ratio was decreased (p<0.05) implying reduced transcriptional activity of GR in MDD patients. MDD subjects had higher cortisol levels than controls and cortisol concentrations were positively correlated with PBMC pGR-S226 levels from the same blood samples. There was no difference in the levels of tGR between MDD and control subjects. The study showed that altered phosphorylation of GR could contribute to impaired GR function related to the pathophysiology of depression.
authors.affiliation: Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, P.O. Box-522-MBE090, 11001 Belgrade, Serbia.
authors.forename: Iva
authors.initials: I
authors.lastname: Simic
authors.forename: Nadja P
authors.initials: NP
authors.lastname: Maric
authors.forename: Milos
authors.initials: M
authors.lastname: Mitic
authors.forename: Ivan
authors.initials: I
authors.lastname: Soldatovic
authors.forename: Zorana
authors.initials: Z
authors.lastname: Pavlovic
authors.forename: Marina
authors.initials: M
authors.lastname: Mihaljevic
authors.forename: Sanja
authors.initials: S
authors.lastname: Andric
authors.forename: Marija B
authors.initials: MB
authors.lastname: Radojcic
authors.forename: Miroslav
authors.initials: M
authors.lastname: Adzic
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone