Tasker Jeffrey G
Neurobiology Division, Department of Cell and Molecular Biology, Tulane University, 2000 Percival Stern Hall, New Orleans, LA 70118, USA.
Obesity (Silver Spring). 2006 Aug;14 Suppl 5:259S-265S. doi: 10.1038/oby.2006.320.
The hypothalamic paraventricular nucleus (PVN) is a major integrative site for the control of homeostasis, including energy balance, through coordinated regulation of neuroendocrine and autonomic outputs. However, cross-talk regulation of PVN neuroendocrine and preautonomic systems is poorly understood. The stress response invokes the coordinated control of motor, hormonal, and vegetative systems to establish homeostasis after an environmental perturbation. Elevated stress levels of circulating glucocorticoids give rise to multiple, complex physiological effects. The complexity of the glucocorticoid actions is caused by the wide range of glucocorticoid target tissues and to the broad time scale over which the actions occur. Recent studies have revealed rapid glucocorticoid actions in the hypothalamus that may provide an integrative signal linking stress with the regulation of energy and fluid homeostasis. Glucocorticoids inhibit PVN and supraoptic nucleus neurons by stimulating a rapid synthesis and retrograde release of endocannabinoids, which suppress synaptic excitation through presynaptic CB1 receptor activation. The glucocorticoid-induced endocannabinoid synthesis is mediated apparently by a novel membrane-associated glucocorticoid receptor found in multiple subpopulations of hypothalamic neuroendocrine cells. It may, therefore, represent a mechanism for rapid glucocorticoid control of activity among different neuroendocrine systems to coordinate a global response to stress. In support of this, leptin, a circulating adipose signal that regulates food intake and energy expenditure through central actions, blocks the glucocorticoid-mediated endocannabinoid release in the PVN. This represents a means by which the regulation of stress and feeding may interface in the PVN, thus providing a possible mechanism for the integration of multiple homeostatic functions.
下丘脑室旁核（PVN）是通过对神经内分泌和自主神经输出的协调调节来控制体内平衡（包括能量平衡）的主要整合部位。然而，PVN神经内分泌系统和自主神经前体系统的相互调节却鲜为人知。应激反应会引发运动、激素和植物神经系统的协同控制，以便在环境扰动后建立体内平衡。循环糖皮质激素应激水平升高会产生多种复杂的生理效应。糖皮质激素作用的复杂性是由糖皮质激素靶组织的广泛范围以及作用发生的广泛时间尺度引起的。最近的研究揭示了下丘脑内糖皮质激素的快速作用，这可能提供了一个将应激与能量和液体平衡调节联系起来的整合信号。糖皮质激素通过刺激内源性大麻素的快速合成和逆向释放来抑制PVN和视上核神经元，内源性大麻素通过突触前CB1受体激活来抑制突触兴奋。糖皮质激素诱导的内源性大麻素合成显然是由在下丘脑神经内分泌细胞多个亚群中发现的一种新型膜相关糖皮质激素受体介导的。因此，它可能代表了一种糖皮质激素快速控制不同神经内分泌系统活动以协调对应激的整体反应的机制。支持这一观点的是，瘦素是一种通过中枢作用调节食物摄入和能量消耗的循环脂肪信号，它能阻断PVN中糖皮质激素介导的内源性大麻素释放。这代表了应激调节和进食调节在PVN中可能相互作用的一种方式，从而为多种体内平衡功能的整合提供了一种可能的机制。
