title: Glucocorticoid receptor mediates the expansion of splenic late erythroid progenitors during chronic psychological stress.
abstract: Stress evokes an integrated neuroendocrine response perturbing the homeostasis of different physiological systems. In contrast to well established physiologica linteractions between neuroendocrine and immune systems during chronic stress, there has been relatively little information on the effects of psychological stress on erythroid cells. Since stress-induced erythropoiesis occurs predominantly in the spleen, in the current study, we investigated the influence of chronic psychological stress on splenic erythroid progenitors and examined a role of glucocorticoid receptor (GR) in observed effect using a mouse model of restraint. The adult male mice were subjected to 2 hours daily restraint stress for 7 or 14 consecutive days and the role of GR in erythropoietic response to stress was assessed by pretreatment of mice with GR antagonist mifepristone 60 min prior to restraint. The results showed that chronic restraint stress induced an increase in spleen weight as well as in the cellularity of red pulp, as compared to controls. Furthermore, 7 and 14 days of restraint stress resulted in markedly increased number of both splenic early (BFU-E) and late (CFU-E) erythroid progenitors. Blockade of GR with mifepristone did not affect the number of BFU-E in stressed mice, but it completely abolished the effect of repeated psychological stress on CFU-E cells. Additionally, plasma corticosterone concentration was enhanced whereas the GR expression was significantly decreased within splenic red pulp after one and two weeks of stress exposure. Obtained findings suggest for the first time an indispensable role for GR in the expansion of CFU-E progenitors in the spleen under conditions of chronic psychological stress.
authors.affiliation: University of Belgrade, Institute for Medical Research, Belgrade, Serbia. mirelab@imi.bg.ac.rs.
authors.forename: S
authors.initials: S
authors.lastname: Vignjevic
authors.forename: M
authors.initials: M
authors.lastname: Budec
authors.forename: D
authors.initials: D
authors.lastname: Markovic
authors.forename: D
authors.initials: D
authors.lastname: Dikic
authors.forename: O
authors.initials: O
authors.lastname: Mitrovic
authors.forename: M
authors.initials: M
authors.lastname: Diklic
authors.forename: T
authors.initials: T
authors.lastname: Suboticki
authors.forename: V
authors.initials: V
authors.lastname: Cokic
authors.forename: G
authors.initials: G
authors.lastname: Jovcic
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D003348:Cortisone / Q000097:blood; D004195:Disease Models, Animal; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008808:Mice, Inbred CBA; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012149:Restraint, Physical; D015398:Signal Transduction; D013154:Spleen / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D003348:Cortisone