Laryea Gloria, Muglia Lisa, Arnett Melinda, Muglia Louis J
Neuroscience Graduate Program, School of Medicine, Vanderbilt University, Nashville, TN, United States; Center for Preterm Birth Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 7009, Cincinnati, OH 45229, United States.
Center for Preterm Birth Research, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 7009, Cincinnati, OH 45229, United States.
Front Neuroendocrinol. 2015 Jan;36:150-64. doi: 10.1016/j.yfrne.2014.09.002. Epub 2014 Sep 27.
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.
糖皮质激素（GC）合成与分泌的负反馈调节通过糖皮质激素受体（GR）在下丘脑-垂体-肾上腺（HPA）轴以及海马体、前额叶皮质和交感神经系统等脑区的功能来实现。GR在负反馈中的这一功能协调基础糖皮质激素分泌以及应激诱导的分泌增加，从而将GC产生与应激源的强度和持续时间整合起来。本综述描述了GR缺失在包括全脑、下丘脑室旁核（PVN）和垂体在内的主要负反馈位点的影响。在基因小鼠模型中，我们评估HPA轴的昼夜节律调节、应激刺激的神经内分泌反应和行为活动，以及机体代谢的综合反应。我们的分析提供了关于区域特异性GR介导的负反馈作用的信息，以深入了解HPA轴失调以及精神和代谢紊乱的发病机制。
