GROWTH HORMONE AND SEX STEROID EFFECTS ON SKELETAL MUSCLE IN OLDER WOMEND & MEN

生长激素和性类固醇对老年女性骨骼肌的影响

• 批准号: 6121394
• 负责人: Marc Roy Blackman
• 金额: $ 6.52万
• 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: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121394
• 关键词: adipose tissue; aging; bone metabolism; cardiovascular function; clinical research; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; insulinlike growth factor; muscle function; muscle metabolism; muscle strength; outcomes research; placebos; respiratory function; sex hormones; somatotropin; striated muscles

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 effects to increase muscle mass and strength, decrease body fat, and increase aerobic capacity. We have been 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.

人类的衰老通常伴随着各种因素的逐渐减少。 生理功能，这在一些人身上导致了生理上的 损害，并最终可能导致残疾，从而恶化 生活质量和独立性受到限制。正常衰老也经常发生。 与循环中生长激素(GH)、胰岛素水平降低有关- 如生长因子-I(IGF-I)和性类固醇激素；肌肉减少 体重和力量，以及增加总脂肪和腹内脂肪。治疗 使用重组人生长激素或性激素可以改善身体状况 一些老年人的成分，但这种荷尔蒙的影响 对各种生理功能的单独或联合治疗 仍有待定义。 我们假设与年龄相关的生长激素、胰岛素样生长因子-I和性激素的减少 单独和交互作用导致骨骼肌块减少 和力量，增加身体脂肪，降低老年人的有氧能力 以及恢复正常生长激素、胰岛素样生长因子-I和性类固醇 联合激素治疗的状态将产生相加效应以增加 肌肉质量和力量，减少身体脂肪，增加有氧能力。 我们一直在进行一项安慰剂对照的双掩蔽研究 一群健康的、能走动的、居住在社区之外的男女 65岁，IGF-I和性激素水平低，以确定是否 6个月单用重组人生长激素，单用性类固醇激素 (女性为雌激素/孕激素，男性为睾丸素)，或联合使用重组人生长激素 外加性类固醇会增加或改善骨骼肌群，力量， 和全身蛋白质合成，减少总脂肪和腹部脂肪；以及 改善有氧能力和心血管功能，以及选择 内分泌、代谢、免疫学、皮肤科和心理行为学 功能。我们还使用聚合酶链式反应技术评估生长激素和生长激素的mRNAs。 骨骼肌活检中的IGF-I受体、IGF-I和IGF-I结合蛋白 样品；以及后一种分子事件与 某些生理结果变量。