The effect of ghrelin, leptin and orexins on the function of pituitary somatotropes in rat, mouse and human.

营养不良，如肥胖或消耗综合征是伴随着生长激素缺乏。三种新发现的代谢调节激素——来自脂肪组织的瘦素、来自胃的胃饥饿素和来自下丘脑的食欲素，在调节食欲、能量消耗和肥胖方面发挥着重要作用。三种代谢调节激素的受体都存在于垂体生长激素分泌细胞中，积累的实验室数据表明，三种激素可以改变生长激素的分泌。然而，报告的结果却相互矛盾。这三种激素的作用机制尚不清楚，代谢调节激素与生长激素内在调节系统的相互关系尚不清楚。我们建议通过研究瘦素、饥饿素和食欲素在小鼠体内治疗和体外培养垂体细胞治疗的效果来澄清这一问题。测量垂体生长激素分泌、生长激素和GH调节激素受体合成。我们还将利用GH-GFP转基因小鼠，在体内对生长色素进行特异性绿色荧光信号标记，研究体内处理后小鼠垂体生长色素的形态学变化。通过完成这个项目，我们将能够(1)阐明代谢调节激素在控制生长激素水平中的生理作用，(2)阐明代谢调节激素在营养不良条件下发生的生长激素缺乏中的病理作用。

Malnutrition such as obesity or wasting syndrome is accompanied by GH deficiency. Three newly discovered metabolic regulatory hormones, leptin from fat tissue, ghrelin from stomach and orexins from hypothalamus, play important roles in regulating appetite, energy expenditure, and adiposity. Receptors for three metabolic regulatory hormones are all present in pituitary GH secreting cells (somatotropes) and accumulated laboratory data indicate a modification of GH secretion by three hormones. Contradictory results have however been reported. Mechanisms of action of these three hormones are not clear and the interrelationship between metabolic regulatory hormones and intrinsic GH regulatory system is unknown. We propose to clarify this issue by investigating the effect of in vivo treatment of mice and in vitro treatment of cultured pituitary cells with leptin, ghrelin, and orexins. GH secretion, GH and GH-regulatory hormones' receptor synthesis in pituitary somatotropes will be measured. We will also use GH-GFP transgenic mice, in which somatotropes are specifically marked with green fluorescent signal, to study morphological change of somatotropes in mouse pituitary glands after in vivo treatment. By completing this project, we will be able (1) to clarify the physiological role of metabolic regulatory hormones in control of GH levels and (2) to clarify the pathological role of metabolic regulatory hormones in GH deficiency occurred in malnutritional conditions.