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Publication : The role of the forebrain glucocorticoid receptor in acute and chronic stress.

First Author  Furay AR Year  2008
Journal  Endocrinology Volume  149
Issue  11 Pages  5482-90
PubMed ID  18617609 Mgi Jnum  J:145489
Mgi Id  MGI:3834810 Doi  10.1210/en.2008-0642
Citation  Furay AR, et al. (2008) The role of the forebrain glucocorticoid receptor in acute and chronic stress. Endocrinology 149(11):5482-90
abstractText  Previous work has implicated the forebrain glucocorticoid receptor (GR) in feedback regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present series of experiments used male mice with a targeted forebrain-specific GR knockout (in which forebrain includes the prefrontal cortex, hippocampus, and basolateral amygdala) to determine the role of forebrain GR in HPA axis regulation after stress. The data indicate that the forebrain GR is necessary for maintaining basal regulation of corticosterone secretion in the morning, confirming its role in HPA axis regulation. Our data further indicate that the forebrain GR is necessary for negative feedback after both mild and robust acute psychogenic stressors but not hypoxia, a systemic stressor. In contrast, forebrain-specific GR knockout and control mice exhibit equivalent HPA axis hyperactivity and facilitation after chronic variable stress, suggesting that changes in forebrain GR are not essential for chronic stress-induced pathology. These studies provide novel and definitive evidence that the forebrain GR selectively contributes negative feedback regulation of HPA axis responses to psychogenic stressors. Moreover, the data indicate that chronic stress-induced alterations in HPA axis function are mediated by mechanisms independent of the forebrain GR. Overall, the data are consistent with an essential role of the forebrain GR in coordinating endocrine responses to stimuli of a psychological origin.
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