SCREENING FOR GROWTH HORMONE AND SEX STEROID EFFECTS

筛选生长激素和性类固醇效应

• 批准号: 6281949
• 负责人: Marc Roy Blackman
• 金额: $ 5.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281949
• 关键词: aging; body composition; cardiovascular function; clinical research; clinical trials; estrogens; functional ability; hormone therapy; human old age (65+); human subject; human therapy evaluation; insulinlike growth factor; progesterone; respiratory function; sex hormones; somatotropin; testosterone

Human aging is generally accompanied by a gradual decline in various physiological functions, which in some people results in physical impairments, and ultimately may cause disabilities which worsen the quality of life and limit independence. Normal aging is also frequently associated with reduced circulating levels of growth hormone (GH), insulin-like growth factor-I (IGF-I, and sex steroid hormones; decreased muscle mass and strength; and increased total and intra-abdominal fat. Treatment with recombinant human GH (rhGH) or sex steroids can improve body composition in some older persons, yet the effects of such hormonal treatment (singly or in combination) on various physiological functions remain to be defined. We hypothesize that age-related decreases in GH, IGF-I and sex steroids separately and interactively contribute to diminished skeletal muscle mass and strength, increased body fat, and reduced aerobic capacity in elderly women and men; and that restitution of normal GH, IGF-I and sex steroid status by combined hormone therapy will exert additive or synergistic effects to increase muscle mass and strength, decrease body fat, and increase aerobic capacity. Thus, we are now conducting a placebo-controlled, double-masked study in a group of healthy, ambulatory, community-dwelling women and men beyond 65 years of age, with low IGF-I and sex steroid levels, to determine whether 6-months of administration of rhGH alone, sex steroids hormones alone (estrogen/progestin in women and testosterone in men), or combined rhGH plus sex steroids will increase or improve skeletal muscle mass, strength, and total body protein synthesis; decrease total and abdominal fat; and improve aerobic capacity and cardiovascular function, as well as selected endocrine, metabolic, immunological, dermatological, and psychobehavioral functions. We are also using PCR techniques to assess mRNAs for GH and IGF-I receptors, IGF-I, and IGF-I binding proteins in skeletal muscle biopsy specimens; and the relationships between the latter molecular events and certain physiological outcome variables. Should the current study reveal beneficial effects of hormone replacement, then we plan to conduct certain targeted, longer-term investigations to examine the interactions of similar hormone treatments with other interventions (e.g. exercise conditioning), and their effects on functional status measurements, in selected elderly populations.

人类的衰老一般伴随着各种 生理功能，这在某些人中会导致身体 损伤，并最终可能导致残疾， 生活质量和独立性有限。正常的衰老也经常 与生长激素（GH）循环水平降低有关， 胰岛素样生长因子-I（IGF-I）和性类固醇激素;降低 肌肉质量和力量;增加总脂肪和腹内脂肪。 用重组人生长激素（rhGH）或性类固醇治疗可以改善 一些老年人的身体成分，但这种激素的影响， 各种生理功能的治疗（单独或组合） 仍有待确定。我们假设与年龄相关的GH下降， IGF-I和性类固醇分别和交互作用有助于 减少骨骼肌质量和强度，增加身体脂肪， 老年妇女和男子的有氧能力降低; 联合激素治疗可使GH、IGF-I和性类固醇状态正常， 发挥累加或协同作用，以增加肌肉质量， 力量，减少身体脂肪，增加有氧能力。因此，我们 目前正在一组受试者中进行安慰剂对照、双盲研究， 健康，流动，社区居住的妇女和男子超过65岁， 低IGF-I和性类固醇水平，以确定是否6个月 单独给予rhGH，单独给予性类固醇激素 （女性雌激素/睾酮和男性睾酮）或联合rhGH 加上性类固醇将增加或改善骨骼肌质量， 强度和全身蛋白质合成;减少总和腹部 脂肪;提高有氧能力和心血管功能，以及 选择内分泌、代谢、免疫、皮肤病学和 心理行为功能我们还使用PCR技术来评估 生长激素和胰岛素样生长因子-I受体、胰岛素样生长因子-I和胰岛素样生长因子-I结合蛋白的mRNA， 骨骼肌活检标本;以及后者之间的关系 分子事件和某些生理结果变量。如果 目前的研究揭示了激素替代的有益效果，那么我们 计划进行一些有针对性的长期调查， 类似激素治疗与其他干预措施的相互作用 (e.g.运动调节），以及它们对功能状态的影响 在选定的老年人群体中进行测量。