The role of ghrelin in somatopause

生长素释放肽在躯体更年期中的作用

• 批准号: 6870857
• 负责人: ELENI V DIMARAKI
• 金额: $ 14.38万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6870857
• 关键词: age difference; aging; bioperiodicity; blood chemistry; clinical research; estrogens; fasting; follicle stimulating hormone; gender difference; ghrelin; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; nutrition related tag; postmenopause; somatotropin; young adult human (21-34)

DESCRIPTION (provided by applicant): Somatopause, the decline of growth hormone (GH) with aging, is due to decreased GH pulse amplitude and might contribute to many of the manifestations of aging. To explain somatopause, one needs to study the regulation of pulsatile GH secretion across the life span. In men but not in women, there is decline of the hypothalamic GH-releasing hormone (GHRH) with aging. The hypothesis of this study is that decreased output of ghrelin, a potent GH secretagogue of gastric origin, contributes to somatopause, and that its role is more prominent in women than in men. The decrease in estrogen levels in menopause might also contribute to somatopause in women and this effect could be mediated through reducing GH secretion. To test the role of ghrelin in somatopause, 12 young women, 12 older menopausal women, 12 young men and 12 older men will be studied. All research participants will be admitted to the General Clinical Research Center for 4 days. After they have blood sampling every 10 min for 24 h to measure ghrelin and GH, they will fast for one day and then blood drawing every 10 min for 24 h will be repeated. Young and older women will be studied twice, during an "estrogen-poor" period and during an "estrogen-rich" period that will be created by transdermal estrogen. Young and older men will be studied once. The data will be analyzed to examine the temporal relationships between ghrelin and GH concentrations and to differentiate the effects of age, gender, and estrogen status on ghrelin and GH. The response of ghrelin to fasting will be used as an index of ghrelin reserves. These studies will improve our understanding of the GH changes with aging and will examine the role of ghrelin in GH secretion regulation across the life span. They will also test whether estrogen levels have an effect on ghrelin secretion. GH is widely marketed anti-aging treatment but the available methods of GH administration do not restore normal youthful GH environment. Understanding the mechanisms of somatopause would result in the design new treatments to restore youthful GH secretion in older individuals.

描述（由申请人提供）：躯体更年期，即生长激素（GH）随着衰老而减少，是由于 GH 脉冲幅度降低造成的，可能导致许多衰老表现。为了解释躯体更年期，我们需要研究整个生命周期中脉动式 GH 分泌的调节。随着年龄的增长，男性下丘脑 GH 释放激素 (GHRH) 会下降，但女性则不然。这项研究的假设是，生长素释放肽（一种来自胃的有效 GH 促分泌素）的分泌量减少会导致躯体更年期，并且其作用在女性中比在男性中更为突出。更年期雌激素水平的下降也可能导致女性出现躯体更年期，这种效应可以通过减少 GH 分泌来介导。为了测试生长素释放肽在躯体更年期中的作用，将对 12 名年轻女性、12 名老年更年期女性、12 名年轻男性和 12 名老年男性进行研究。所有研究参与者将被送往普通临床研究中心为期 4 天。在24小时内每10分钟抽血一次以测量ghrelin和GH后，他们将禁食一天，然后重复24小时内每10分钟抽血一次。年轻和老年女性将接受两次研究，一次是“雌激素缺乏”时期，另一次是通过透皮雌激素产生的“雌激素丰富”时期。年轻和年长的男性将被研究一次。将分析数据以检查生长素释放肽和生长激素浓度之间的时间关系，并区分年龄、性别和雌激素状态对生长素释放肽和生长激素的影响。胃饥饿素对禁食的反应将被用作胃饥饿素储备的指标。 这些研究将增进我们对 GH 随着衰老而变化的理解，并将研究 ghrelin 在整个生命周期中 GH 分泌调节中的作用。他们还将测试雌激素水平是否对生长素释放肽分泌有影响。 GH 是广泛销售的抗衰老治疗方法，但现有的 GH 给药方法并不能恢复正常的年轻 GH 环境。了解躯体更年期的机制将有助于设计新的治疗方法，以恢复老年人年轻时的 GH 分泌。