Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Fujimiya M, Katsuura G, Makino S, Fujino M A, Kasuga M
Second Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.
Neuroendocrinology. 2001 Sep;74(3):143-7. doi: 10.1159/000054680.
Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, was recently identified in the rat stomach. Previous studies have shown that ghrelin potently increases growth hormone release and food intake. We examined the effects of the gastric peptide ghrelin on anxiety-like behavior in association with the hypothalamic-pituitary-adrenal axis in mice. Both intra-third cerebroventricular and intraperitoneal administration of ghrelin potently and significantly induced anxiogenic activities in the elevated plus maze test. Ghrelin gene expression in the stomach was increased by tail pinch stress as well as by starvation stress. Administration of a corticotropin-releasing hormone (CRH) receptor antagonist significantly inhibited ghrelin-induced anxiogenic effects. Peripherally administered ghrelin significantly increased CRH mRNA, but not urocortin mRNA expression in the hypothalamus. Furthermore, intraperitoneal injection of ghrelin produced a significant dose- dependent increase in serum corticosterone levels. These findings suggest that ghrelin may have a role in mediating neuroendocrine and behavioral responses to stressors and that the stomach could play an important role, not only in the regulation of appetite, but also in the regulation of anxiety.
胃饥饿素是生长激素促分泌素受体的内源性配体，最近在大鼠胃中被发现。先前的研究表明，胃饥饿素能有效增加生长激素释放和食物摄入量。我们研究了胃肽胃饥饿素对小鼠焦虑样行为的影响及其与下丘脑 - 垂体 - 肾上腺轴的关系。在高架十字迷宫试验中，经第三脑室和腹腔注射胃饥饿素均能有效且显著地诱导焦虑活性。尾部夹捏应激和饥饿应激均可使胃中胃饥饿素基因表达增加。给予促肾上腺皮质激素释放激素（CRH）受体拮抗剂可显著抑制胃饥饿素诱导的焦虑效应。外周给予胃饥饿素可显著增加下丘脑CRH mRNA表达，但不增加尿皮质素mRNA表达。此外，腹腔注射胃饥饿素可使血清皮质酮水平呈显著剂量依赖性升高。这些发现表明，胃饥饿素可能在介导对应激源的神经内分泌和行为反应中起作用，并且胃不仅在食欲调节中，而且在焦虑调节中可能发挥重要作用。
