HORMONES, HORMONE RECEPTORS AND AGING.III--AGING AND HUMAN ENDOCRINE REGULATION

激素、激素受体与衰老III--衰老与人体内分泌调节

• 批准号: 3802181
• 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/3802181
• 关键词: adrenocorticotropic hormone; aging; arginine; blood chemistry; body composition; cortisol; dexamethasone; drug administration routes; glucocorticoids; growth hormone releasing hormone; hormone metabolism; hormone receptor; hormone regulation /control mechanism; human old age (65+); human subject; human therapy evaluation; hypothalamic pituitary axis; insulinlike growth factor; lysine; oral administration; pituitary adrenal axis; somatotropin; young adult human (21-34)

Results of a study quantitating the effects of aging on the regulation of the hypothalamic-pituitary-adrenal axis were submitted and published in FY 91. This work showed that both spontaneous 24 h pulsatile and CRH- stimulated secretion of ACTH and cortisol were unchanged with age and responded similarly in young and old men to suppression with graded doses of dexamethasone. These data do not support the hypothesis, advanced by others, that age-related changes in body composition and metabolism are due to a loss of sensitivity of the hypothalamic-pituitary-adrenal axis to negative feedback by glucocorticoids with resultant glucocorticoid excess. We are currently investigating the relationship of GH deficiency to aging and testing the effectiveness of potential interventions for raising endogenous GH and IGF-I secretion in older people. A study of 24 hr pulsatile GH secretion, acute GH response to iv GHRH, and plasma IGF-I measurements, done before and after two weeks of twice daily GHRH injections, repeated at 2 different doses, has been completed in 10 old and 9 young men. We demonstrated that pulsatile GH secretion and serum IGF-I levels were low in older men, and increased into the range seen in normal young men after treatment with 2 mg of GHRH daily. A manuscript is in preparation. A similar study of the effects of continuous 24 h subcutaneous GHRH infusion in old vs. young men is in the final stages of completion. A study of the effects of 2 weeks of orally administered 50:50 arginine/lysine mixture on GH and IGF-I secretion in older men is also nearly complete.

一项量化衰老对调节的影响的研究结果 下丘脑-垂体-肾上腺轴在FY提交并发表 91. 这项工作表明，自发的 24 小时脉动和 CRH- 促肾上腺皮质激素和皮质醇的刺激分泌随着年龄的增长而变化 年轻人和老年人对分级剂量抑制的反应相似 地塞米松。 这些数据不支持由 其他人认为，与年龄相关的身体成分和新陈代谢的变化是由于 下丘脑-垂体-肾上腺轴敏感性丧失 糖皮质激素的负反馈导致糖皮质激素过量。 我们目前正在研究 GH 缺乏与衰老的关系 并测试潜在干预措施的有效性 老年人的内源性 GH 和 IGF-I 分泌。 24小时研究 脉动 GH 分泌、对 iv GHRH 的急性 GH 反应和血浆 IGF-I 测量，在每天两次 GHRH 两周之前和之后进行 已完成 10 名老年人和 10 名儿童的注射，重复 2 次不同剂量。 9个年轻人。 我们证明了脉动 GH 分泌和血清 IGF-I 老年男性的水平较低，并增加到正常人的范围内 每天接受 2 毫克 GHRH 治疗后的年轻男性。 手稿在 准备。 连续24小时效果的类似研究 老年男性与年轻男性的皮下 GHRH 注射正处于最后阶段 完成。 50:50口服2周效果研究 精氨酸/赖氨酸混合物对老年男性 GH 和 IGF-I 分泌的影响 几乎完成。