NEUROENDOCRINE CONTROL OF THE STRESS RESPONSE

研究主要集中在下丘脑和下丘脑的调节机制。 应激状态下的脑垂体功能。研究表明，这种水平 脑垂体促肾上腺皮质激素反应的差值是由微分决定的 下丘脑调节激素促肾上腺皮质激素释放激素的调节 促肾上腺皮质激素释放激素和加压素与糖皮质激素的敏感性 反馈。而渗透过程中对HPA轴的抑制 与大细胞神经元刺激VP分泌有关 下丘脑室旁核和视上核， 促肾上腺皮质激素相关的生理-心理应激范式 高反应性表现为CRH和CRH/VP小细胞活化 室旁核内的神经元。 大鼠脑垂体前膜与[~3H]VP结合的研究 在渗透胁迫下(缺水和2%的盐水摄入量)或 生理-心理应激(固定或I.P.高渗盐水 注射)显示垂体VP的变化之间有很好的相关性 受体和促肾上腺皮质激素反应性。VP的Northern杂交分析 慢性应激大鼠脑垂体受体基因表达的研究 MRNA水平的变化与VP结合时的变化平行。与之形成鲜明对比的是 在慢性应激、脑下垂体持续暴露于 巨细胞VP手术分流可提高VP水平 垂体门循环引起促肾上腺皮质激素脱敏和 垂体VP受体下调。这些数据表明，监管 受体数目的变化在调节血管紧张素转换酶的活性中起关键作用 慢性应激时促肾上腺皮质激素的反应性。 对CRH受体在大脑中表达的研究表明， 而CRH结合和CRH受体mRNA在下丘脑室旁核中未检测到 在基础条件下，它们在应激过程中显著增加，并在 生理心理应激后的小细胞 渗透刺激后的巨细胞细胞。这些数据表明 CRH在PVN功能调控中的自身调节作用。

Research has focused on the mechanism of regulation of hypothalamic and pituitary function during stress. The studies have shown that the level of response of the pituitary corticotroph is determined by differential regulation of the hypothalamic regulators corticotropin releasing hormone (CRH) and vasopressin (VP) and the sensitivity of the glucocorticoid feedback. While the inhibition of the HPA axis during osmotic is associated with stimulation of VP secretion by magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei of the hypothalamus, physical-psychological stress paradigms associated with corticotroph hyperresponsiveness show activation of CRH and CRH/VP parvicellular neurons in the PVN. Binding studies using [3H]VP and anterior pituitary membranes from rats under osmotic stress (water deprivation and 2% saline intake) or physical-psychological stress (immobilization or i.p. hypertonic saline injection) showed a good correlation between changes in pituitary VP receptors and corticotroph responsiveness. Northern blot analysis of VP receptor mRNA in pituitaries from chronically stressed rats revealed changes in mRNA levels parallel to those in VP binding. In contrast to the findings in chronic stress, continuous exposure of the pituitary to increased levels of VP by surgical shunting of magnocellular VP to the hypophyseal portal circulation caused corticotroph desensitization and pituitary VP receptor downregulation. These data suggest that regulation of VP receptor number plays a critical role in the regulation of corticotroph responsiveness during chronic stress. Studies on the expression of CRH receptors in the brain revealed that while CRH binding and CRH receptor mRNA are undetectable in the PVN under basal conditions, they markedly increase during stress with expression in parvicellular cells after physical psychological stress and in magnocellular cells after osmotic stimulation. These data suggest an autoregulatory role for CRH in the control of PVN function.