HORMONES, HORMONE AND AGING

荷尔蒙、荷尔蒙与衰老

• 批准号: 3808839
• 负责人: S MITCHELL HARMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3808839
• 关键词: aging; blood chemistry; blood pressure; bone metabolism; calcium metabolism; cholesterol; coronary disorder; disease /disorder proneness /risk; estrogens; follicle stimulating hormone; gonadotropins; growth hormone releasing hormone; hormone metabolism; hormone receptor; hormone regulation /control mechanism; human middle age (35-64); human old age (65+); human subject; hypothalamic pituitary axis; immunochemistry; longitudinal human study; luteinizing hormone; menopause; osteoporosis; pituitary adrenal axis; pituitary gonadal axis; postmenopause; progesterone; radioimmunoassay; sex hormones; somatotropin; testosterone

Continuation of this project in FY-90 has included completion of a study of the interaction of age and transdermal estradiol replacement at 3 different doses in 28 postmenopausal women, investigating effects of estrogen with and without progestogen on basal growth hormone (GH) and IGF-1, GH responses to GHRH, as well as calciotropic and gonadotropic hormone regulation. We found: (1) older women remain responsive to the bone- conserving action of estrogen; and (2)estrogens' action to preserve bone mass appears to be independent of any modulation of GH, IGF-1, or calcitonin secretion. A study to quantitate the effects of aging on the regulation of the hypothalamic-pituitary-adrenal axis has also been completed in 11 young and 11 older men, using overnight monitoring of pituitary-adrenal function with 12 hours of every 10-minute blood samples followed by CRH stimulation tests under basal conditions and then 4 hours of every 10-minute blood sampling followed by CRH stimulation tests repeated at weekly intervals during ACTH suppression with each of 3 doses of dexamethasone. Results showed that both spontaneous and CRH-stimulated secretion of ACTH and cortisol were unchanged with age and responded similarly to suppression with graded doses of dexamethasone. These findings provide strong evidence against the hypothesis that an age-related loss of sensitivity of the hypothalamic-pituitary-adrenal axis to negative feedback by glueocorticoids leads to glucocorticoid excess and resultant changes in body composition and metabolism. A new study using 24 hr. monitoring of spontaneous pulsatile GH secretion, acute GH response to iv GHRH, and plasma IGF-I measurements, all done before after two weeks of chronic GHRH injections repeated at 2 different doses, has been initiated in order to investigate the relationship of GH deficiency to aging and to test the effectiveness of possible interventions for raising GH and IGF-I secretion in older people.

90 财年继续开展该项目包括完成一项研究 年龄和透皮雌二醇替代疗法在 3 个不同条件下的相互作用 对 28 名绝经后妇女进行剂量研究，调查雌激素的影响 基础生长激素 (GH) 和 IGF-1、GH 不含孕激素 对 GHRH 以及促钙激素和促性腺激素的反应 规定。我们发现：（1）老年女性仍然对骨骼敏感 保存雌激素的作用； (2)雌激素保护骨骼的作用 质量似乎与 GH、IGF-1 或 降钙素分泌。一项量化衰老对人的影响的研究 下丘脑-垂体-肾上腺轴的调节也已被证实 通过夜间监测，对 11 名年轻男性和 11 名老年男性完成了这项研究 每 10 分钟血样 12 小时的垂体-肾上腺功能 随后进行基础条件下的CRH刺激测试，然后4小时 每 10 分钟抽血一次，然后进行 CRH 刺激测试 在 ACTH 抑制期间，每周重复 3 剂 地塞米松。结果表明，自发的和 CRH 刺激的 ACTH 和皮质醇的分泌量随年龄变化而变化，并有反应 与分级剂量的地塞米松抑制类似。这些发现 提供了强有力的证据来反对以下假设：与年龄相关的丧失 下丘脑-垂体-肾上腺轴对负反馈的敏感性 糖皮质激素导致糖皮质激素过量并由此产生的变化 身体成分和新陈代谢。一项新研究使用 24 小时。监测 自发性脉动 GH 分泌、对 iv GHRH 的急性 GH 反应，以及 血浆 IGF-I 测量，均在慢性 GHRH 两周后进行 已开始以 2 种不同剂量重复注射，以便 研究 GH 缺乏与衰老的关系并测试 提高 GH 和 IGF-I 分泌的可能干预措施的有效性 在老年人中。