Dallman Mary F, Akana Susan F, Laugero Kevin D, Gomez Francisca, Manalo Sotara, Bell M E, Bhatnagar Seema
Department of Physiology, University of California San Francisco, Box 0444, San Francisco, CA 94143-0444, USA.
Physiol Behav. 2003 Jun;79(1):3-12. doi: 10.1016/s0031-9384(03)00100-8.
To begin to understand the effects of chronic stress on food intake and energy stores, the effects of increased activity in the hypothalamo-pituitary-adrenal (HPA) axis and glucocorticoids (GCs) on the body and brain must first be understood. We propose two major systems that are both GC sensitive: a metabolic feedback that is inhibitory and a direct central GC drive. Under basal conditions, the metabolic feedback signal to brain is dominant, although infusion of GC into a lateral brain ventricle blocks the effects of the metabolic feedback. Chronic stress activates GC secretion and brain nuclear GC receptor occupancy, markedly changing the normal relationships between these two major corticosteroid-activated systems. The stressor-induced switch in the relative strengths of these signals determines subsequent brain regulation of stress responses (behavioral, neuroendocrine and autonomic outflows). The metabolic feedback effects of GCs are mimicked by voluntary sucrose ingestion in adrenalectomized rats, and experiments suggest that the metabolic feedback also inhibits the stressor-induced direct GC drive on brain. We speculate that the interaction between peripheral and central GC-sensitive signaling systems may be coupled through the inhibitory actions of endogenous opiatergic inputs on corticotropin-releasing factor (CRF) neurons.
为了开始理解慢性应激对食物摄入和能量储存的影响，必须首先了解下丘脑 - 垂体 - 肾上腺（HPA）轴活性增加和糖皮质激素（GCs）对身体和大脑的影响。我们提出两个主要的对GC敏感的系统：一个是具有抑制作用的代谢反馈系统，另一个是直接的中枢GC驱动系统。在基础条件下，向大脑传递的代谢反馈信号占主导地位，尽管向侧脑室注入GC会阻断代谢反馈的作用。慢性应激会激活GC分泌并使脑细胞核GC受体占有率增加，从而显著改变这两个主要的皮质类固醇激活系统之间的正常关系。应激源引起的这些信号相对强度的转变决定了随后大脑对应激反应（行为、神经内分泌和自主神经输出）的调节。在肾上腺切除的大鼠中，自愿摄入蔗糖可模拟GC的代谢反馈作用，并且实验表明，代谢反馈也会抑制应激源诱导的大脑直接GC驱动。我们推测，外周和中枢GC敏感信号系统之间的相互作用可能通过内源性阿片能输入对促肾上腺皮质激素释放因子（CRF）神经元的抑制作用而耦合。
