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） 正常衰老过程中分泌减少，导致循环降低 胰岛素样生长因子 (IGF-1) 水平。 虽然生理上 生长激素功能下降的后遗症尚未完全了解，许多 正常衰老中观察到的分解代谢变化，包括骨质减少、肌肉减少 萎缩和运动耐量下降可能部分是由 GH-IGF-I 轴的作用减弱。 与年龄相关的下降 下丘脑-生长激素-IGF 轴的活动可能因此导致 导致老年人跌倒、骨折和虚弱的分解代谢素质， 一种被称为“躯体停经”的综合症。 以前的工作 已证明 GH 和 IGF-I 可以减少脂肪量，增加瘦体重 质量和氮保留，促进全身和骨骼肌净 蛋白质合成。 GH 和高剂量 IGF-1 均可增加重塑骨的出生率。 然而，低剂量的 IGF-I 可能会直接增加成骨细胞功能，而不需要 增加骨吸收，因此可能提供一种有用的方法 增加骨量。 此外，IGF-I 可能具有增强情绪的作用 老年。 为了确定延长 GH 和 IGF-I 的效果 治疗并了解其背后的内分泌机制 生理效应，三项独立的生理学研究 提出了 GH 和 IGF-I 疗法在躯体更年期中的作用。 在这些 研究中，重点将放在理解相互作用 雌激素/孕激素替代疗法（HRT）和治疗 躯体暂停。 研究 1 为期一年，双盲，随机， 安慰剂对照试验将探讨 GH、IGF-I 的相互作用 和雌激素/孕激素治疗对身体成分、肌肉力量和 肌肉生长因子的合成。 研究二将探讨内分泌机制 GH 和 IGF-I 治疗对体液室的影响的基础 细节。 这个实验将建立在之前的研究的基础上，这些研究出乎意料地 证明这两种激素都会导致水分急剧转移到体内 细胞内空间。 研究 III 是一项短期研究，将检验 GH 和 IGF-1 在蛋白质和脂质代谢中的作用，以了解 这些激素在老年女性中的合成代谢作用。 这项研究将有助于 为研究 I 中获得的发现提供了机制基础。这些 研究将首次调查激素相互作用 躯体更年期（GH 和 IGF-I）和更年期的替代疗法 （雌激素和孕激素）并将导致新的药理学方法 治疗老年人体弱。