Chronic restraint stress upregulates erythropoiesis through glucocorticoid stimulation

• Published in: PloS one 2013-10, Vol.8 (10), p.e77935-e77935
• Main Authors: Voorhees, Jeffrey L, Powell, Nicole D, Moldovan, Leni, Mo, Xiaokui, Eubank, Timothy D, Marsh, Clay B
• Format: Article
• Language: English
• Subjects: Analysis; Animal models; Animal tissues; Animals; Biomarkers - metabolism; Blood; Blotting, Western; Cells, Cultured; Chronic Disease; Critical care; Erythrocytes; Erythrocytes - cytology; Erythrocytes - drug effects; Erythrocytes - metabolism; Erythroid Precursor Cells - cytology; Erythroid Precursor Cells - drug effects; Erythroid Precursor Cells - metabolism; Erythropoiesis; Erythropoiesis - drug effects; Erythropoiesis - physiology; Exposure; Female; Females; Gene expression; Gene Expression Profiling; Genomic analysis; Glucocorticoids; Glucocorticoids - metabolism; Heart; Hematology; Hemopoiesis; Homeostasis; Hormone Antagonists - pharmacology; Internal medicine; Iron; Laboratories; Medicine; Mental depression; Mice; Mice, Inbred C57BL; Mifepristone - pharmacology; Oligonucleotide Array Sequence Analysis; Psychological aspects; Psychological stress; Real-Time Polymerase Chain Reaction; Receptors, Glucocorticoid - antagonists & inhibitors; Restraint, Physical; Reticulocytes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Rodents; Steroids (Organic compounds); Stimulation; Stress (Psychology); Stress, Psychological - physiopathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077935

In response to elevated glucocorticoid levels, erythroid progenitors rapidly expand to produce large numbers of young erythrocytes. Previous work demonstrates hematopoietic changes in rodents exposed to various physical and psychological stressors, however, the effects of chronic psychological stress on erythropoiesis has not be delineated. We employed laboratory, clinical and genomic analyses of a murine model of chronic restraint stress (RST) to examine the influence of psychological stress on erythropoiesis. Mice exposed to RST demonstrated markers of early erythroid expansion involving the glucocorticoid receptor. In addition, these RST-exposed mice had increased numbers of circulating reticulocytes and increased erythropoiesis in primary and secondary erythroid tissues. Mice also showed increases in erythroid progenitor populations and elevated expression of the erythroid transcription factor KLF1 in these cells. Together this work reports some of the first evidence of psychological stress affecting erythroid homeostasis through glucocorticoid stimulation.