GH AND IGF-I TREATMENT OF ELDERLY WOMEN

描述（改编自申请人摘要）：生长激素（GH） 在正常衰老过程中分泌下降，导致循环功能降低， 胰岛素样生长因子（IGF-1）。 虽然生理 生长激素功能下降的后遗症尚未完全了解，许多 在正常衰老中看到的分解代谢变化，包括骨质减少，肌肉萎缩， 萎缩和运动耐量下降，可能部分是由于 降低GH-IGF-I轴的作用。 与年龄相关的 下丘脑-生长激素-IGF轴的活动因此可能导致 导致老年人福尔斯、骨折和虚弱的分解代谢素质， 这是一种被称为“躯体疾病”的综合征。 以前的工作 已经证明，GH和IGF-I减少脂肪量，增加瘦体 质量和氮的保留，并促进整个身体和骨骼肌网 蛋白质合成 GH和高剂量IGF-1均能增加骨单位的生成率。 然而，低剂量IGF-I可能直接增加成骨细胞功能， 增加骨吸收，因此可以提供一种有用的手段， 增加骨量。 此外，IGF-I可能具有增强情绪的作用， 老人 为了确定延长GH和IGF-I的影响， 治疗和了解其潜在的内分泌机制， 生理效应，三个独立的研究， GH和IGF-I治疗在躯体疾病中的作用。 在这些 研究，一个主要的重点将放在理解的相互作用， 雌激素/孕激素替代疗法（HRT）和治疗 体细胞死亡 研究1是为期一年的，双盲，随机， 安慰剂对照试验，将探索GH、IGF-I的相互作用 和雌激素/孕酮治疗对身体成分，肌肉力量， 肌肉生长因子合成。 研究II将探索内分泌机制 GH和IGF-I治疗对液体隔室的潜在影响， 详细 这项实验将建立在以前的研究基础上， 表明这两种激素都能引起水的剧烈变化， 胞内空间 第三项研究是一项短期研究， GH和IGF-1在蛋白质和脂质代谢中的作用， 这些激素在老年妇女中的合成代谢作用。 这项研究将帮助 为研究I中的发现提供了机制基础。这些 这些研究将首次对激素和蛋白质之间的相互作用进行研究， 替代疗法的躯体疾病（生长激素和IGF-I）和更年期 （雌激素和孕酮），并将导致新的药理学方法， 老年人虚弱的治疗

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.