GH AND IGF-I TREATMENT OF ELDERLY WOMEN

老年妇女的 GH 和 IGF-I 治疗

• 批准号: 6055379
• 负责人: ANDREW R HOFFMAN
• 金额: $ 25.79万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6055379
• 关键词: aging; body composition; body water; clinical research; clinical trials; estrogens; female; frail elderly; geriatrics; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; insulinlike growth factor; lipid metabolism; muscle strength; osteopenia; postmenopause; progestins; protein metabolism; somatotropin; women's health

DESCRIPTION (Adapted from the Applicant's Abstract): Growth hormone (GH) secretion declines during normal aging, resulting in lower circulating levels of insulin-like growth factor (IGF-1). Although the physiologic sequelae to decreased somatotrope function are not fully understood, many of the catabolic changes seen in normal aging, including osteopenia, muscle atrophy, and decreased exercise tolerance, may in part be caused by the decreased action of the GH-IGF-I axis. The age-related decline in the activity of the hypothalamic-somatotrope-IGF axis may thus result in catabolic diathesis leading to falls, fractures, and frailty in the elderly, a syndrome complex which has been named "the somatopause". Previous work has demonstrated that GH and IGF-I decrease fat mass, increase lean body mass and nitrogen retention, and promote whole body and skeletal muscle net protein synthesis. Both GH and high dose IGF-1 increase the birthrate of remodeling osteons. However, low-dose IGF-I may directly increase osteoblastic function without increasing bone resorption, and may therefore provide a useful means to increase bone mass. Moreover, IGF-I may have mood-enhancing effects in the elderly. In order to determine the effects of prolonged GH and IGF-I therapy and to understand the endocrine mechanisms underlying their physiologic effects, three independent investigations into the physiologic role of GH and IGF-I therapy in the somatopause are proposed. In these studies, a major emphasis will be placed on understanding the interactions of estrogen/progestin hormone replacement therapy (HRT) and treatment of the somatopause. Study 1 is a year long, double-blind, randomized, placebo-controlled trial which will explore the interactions of GH, IGF-I and estrogen/progestin therapy on body composition, muscular strength, and muscle growth factor synthesis. Study II will explore endocrine mechanisms underlying the effects of GH and IGF-I therapy on fluid compartments in detail. This experiment will build upon previous studies which unexpectedly demonstrated that both hormones cause dramatic shifts of water into the intracellular space. Study III is a short term study that will examine the role of GH and IGF-1 in protein and lipid metabolism to understand the anabolic action of these hormones in elderly women. This study will help provide a mechanistic basis for the finding obtained in Study I. These studies will provide the first investigation of the interactions of hormone replacement therapies for the somatopause (GH and IGF-I) and the menopause (estrogen and progestin) and will lead to novel pharmacologic approaches for the treatment of frailty in the elderly.

描述（改编自申请人的摘要）：生长激素（GH） 分泌在正常衰老期间下降，导致较低的循环 胰岛素样生长因子（IGF-1）的水平。 虽然生理 后遗症至降低的体育功能尚未完全了解，许多 正常衰老的分解代谢变化，包括骨质减少，肌肉 萎缩和运动耐受性的降低可能部分是由 GH-IGF-1轴的作用减少。 与年龄有关的下降 因此，下丘脑 - 形成型-IGF轴的活性可能导致 分解代谢素质导致老年人跌倒，骨折和脆弱 综合征综合体，被命名为“ Somapopause”。 以前的工作 已经证明GH和IGF-I减少脂肪质量，增加瘦体 质量和氮保留率，并促进全身和骨骼肌网 蛋白质合成。 GH和高剂量IGF-1都会增加重塑骨的出生率。 但是，低剂量IGF-I可能直接增加成骨细胞功能 增加骨吸收，因此可以提供有用的手段 增加骨骼质量。 此外，IGF-I在 老年。 为了确定延长GH和IGF-I的影响 治疗并了解其基础的内分泌机制 生理效应，三项对生理学的独立研究 提出了GH和IGF-1疗法在体系中的作用。 在这些 研究，将重点放在理解相互作用上 雌激素/孕激素激素替代疗法（HRT）和治疗 躯体。 研究1是一年长的，双盲的，随机的， 安慰剂对照试验将探索GH，IGF-I的相互作用 以及雌激素/孕激素治疗在身体组成，肌肉力量和 肌肉生长因子合成。 研究II将探索内分泌机制 GH和IGF-I治疗对流体室的影响的基础 细节。 该实验将基于以前的研究 证明两种激素都会引起水的急剧转移 细胞内空间。 研究III是一项短期研究，将检查 GH和IGF-1在蛋白质和脂质代谢中的作用以了解 这些激素在老年妇女中的合成代谢作用。 这项研究将有所帮助 为研究I中获得的发现提供了机械基础。 研究将对激素的相互作用进行首次研究 Somaperause（GH和IGF-I）的替代疗法和更年期 （雌激素和孕激素），并将导致新的药理方法 老年人的脆弱疗法。