Bali Anjana, Jaggi Amteshwar Singh
Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala-147002, India.
Curr Drug Targets. 2016;17(5):495-507. doi: 10.2174/1389450116666150518095650.
Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells of gastric oxyntic mucosa to stimulate appetite and food intake along with regulation of growth hormone and insulin secretion; glucose and lipid metabolism; gastrointestinal motility; blood pressure, heart rate and neurogenesis. Furthermore, peripherally (after crossing the blood brain barrier) as well as centrally synthesized ghrelin (in the hypothalamus) regulates diverse functions of central nervous system including stress-associated behavioral functions. Exposure to stress alters the ghrelin levels and alteration in ghrelin levels significantly affects neuro-endocrinological parameters; metabolism-related physiology, behavior and mood. Studies have shown both anxiolytic and anxiogenic role of ghrelin suggesting its dual role in modulating anxiety-related behavior. However, it is proposed that increase in ghrelin levels during stress condition is an endogenous stress coping behavior and increased ghrelin levels may be required to prevent excessive anxiety. In preclinical and clinical studies, an elevation in ghrelin levels during depression has been correlated with their antidepressant activities. Ghrelin-induced modulation of stress and associated conditions has been linked to alteration in hypothalamic-pituitary-adrenal (HPA) axis; autonomic nervous system (mainly sympathetic nervous system and serotonergic neurotransmission. A reciprocal relationship has been reported between corticotropin-releasing hormone (CRH) and ghrelin as ghrelin increases the release of CRH, ACTH and corticosteroids; while CRH decreases the expression of ghrelin. Similarly, ghrelin increases the serotonin turnover and in turn, serotonin controls ghrelin signaling to modulate anxiety-related behavior. The present review discusses the dual role of ghrelin in stress and related behavioral disorders along with possible mechanisms.
胃饥饿素是一种促食欲激素，主要由胃泌酸黏膜的内分泌X/A样细胞合成，可刺激食欲和食物摄入，同时调节生长激素和胰岛素分泌、葡萄糖和脂质代谢、胃肠蠕动、血压、心率和神经发生。此外，外周合成的胃饥饿素（穿过血脑屏障后）以及中枢合成的胃饥饿素（在下丘脑）调节中枢神经系统的多种功能，包括与应激相关的行为功能。暴露于应激会改变胃饥饿素水平，而胃饥饿素水平的改变会显著影响神经内分泌参数、与代谢相关的生理、行为和情绪。研究表明胃饥饿素具有抗焦虑和致焦虑作用，提示其在调节焦虑相关行为中具有双重作用。然而，有人提出在应激状态下胃饥饿素水平升高是一种内源性应激应对行为，可能需要升高的胃饥饿素水平来预防过度焦虑。在临床前和临床研究中，抑郁症期间胃饥饿素水平的升高与其抗抑郁活性相关。胃饥饿素诱导的应激调节及相关情况与下丘脑-垂体-肾上腺（HPA）轴的改变、自主神经系统（主要是交感神经系统和5-羟色胺能神经传递）有关。促肾上腺皮质激素释放激素（CRH）和胃饥饿素之间存在相互关系，因为胃饥饿素会增加CRH、促肾上腺皮质激素（ACTH）和皮质类固醇的释放；而CRH会降低胃饥饿素的表达。同样，胃饥饿素会增加5-羟色胺的周转率，反过来，5-羟色胺会控制胃饥饿素信号传导以调节焦虑相关行为。本综述讨论了胃饥饿素在应激和相关行为障碍中的双重作用及其可能机制。
