期刊
FRONTIERS IN NEUROENDOCRINOLOGY
卷 36, 期 -, 页码 150-164出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yfrne.2014.09.002
关键词
Glucocorticoid receptor; Corticotropin-releasing hormone; Adrenocorticotropic hormone; Corticosterone; Hypothalamic-pituitary-adrenal axis; Paraventricular nucleus of the hypothalamus; Pituitary Circadian regulation; Stress; Metabolism
资金
- NIH [T32 MH064913, R01AMH079010]
- NATIONAL INSTITUTE OF MENTAL HEALTH [T32MH064913, R01MH079010] Funding Source: NIH RePORTER
Negative feedback regulation of glucocorticoid (GC) synthesis and secretion occurs through the function of glucocorticoid receptor (GR) at sites in the hypothalamic-pituitary-adrenal (HPA) axis, as well as in brain regions such as the hippocampus, prefrontal cortex, and sympathetic nervous system. This function of GRs in negative feedback coordinates basal glucocorticoid secretion and stress-induced increases in secretion that integrate GC production with the magnitude and duration of the stressor. This review describes the effects of GR loss along major sites of negative feedback including the entire brain, the paraventricular nucleus of the hypothalamus (PVN), and the pituitary. In genetic mouse models, we evaluate circadian regulation of the HPA axis, stress-stimulated neuroendocrine response and behavioral activity, as well as the integrated response of organism metabolism. Our analysis provides information on contributions of region-specific GR-mediated negative feedback to provide insight in understanding HPA axis dysregulation and the pathogenesis of psychiatric and metabolic disorders. (C) 2014 Elsevier Inc. All rights reserved.
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