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

生长素释放肽、瘦素和食欲素对大鼠、小鼠和人类垂体生长激素功能的影响。

• 批准号: nhmrc : 289311
• 负责人: Prof Chen Chen
• 金额: $ 29.81万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/effect-ghrelin-leptin-mouse-human/82147
• 关键词: effect; ghrelin; leptin; orexins; function

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.

营养不良，如肥胖或消耗综合症，会伴随生长激素缺乏。三种新发现的代谢调节激素，即来自脂肪组织的瘦素、来自胃的生长素释放肽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均存在于垂体 GH 分泌细胞（生长激素）中，并且积累的实验室数据表明三种激素对 GH 分泌的改变。然而，却报道了相互矛盾的结果。这三种激素的作用机制尚不清楚，代谢调节激素与内在 GH 调节系统之间的相互关系也不清楚。我们建议通过研究用瘦素、生长素释放肽和食欲素对小鼠进行体内治疗和对培养的垂体细胞进行体外治疗的效果来澄清这个问题。将测量垂体生长激素中的 GH 分泌、GH 和 GH 调节激素受体的合成。我们还将使用GH-GFP转基因小鼠（生长激素被绿色荧光信号特异性标记）来研究体内治疗后小鼠垂体中生长激素的形态变化。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 GH 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 GH 缺乏中的病理作用。