NIA ACADEMIC AWARD--ANDROGEN ACTION IN THE ELDERLY MALE

NIA 学术奖——雄激素对老年男性的作用

• 批准号: 3078598
• 负责人: JOYCE S. TENOVER
• 金额: $ 5.72万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3078598
• 关键词: aging; androgen inhibitor; blood lipid; blood lipoprotein; body composition; bone density; dihydrotestosterone; enzyme inhibitors; gonadotropins; hormone binding protein; hormone therapy; human old age (65+); human subject; laboratory rat; male; neuropharmacology; physiologic bone resorption; prostate disorder; sex hormones; steroid hormone metabolism; testosterone; urination

Effects of Testosterone (T) Replacement in Elderly Men: Many studies have shown that, as normal men age, there is a gradual decline in testicular function, including a moderate decrease in total serum T and a larger decline in "bioavailable T" (T not bound to sex hormone binding globulin, SHBG). A relationship between this age-related decline in androgen levels and age-related changes in physiological parameters such as serum lipids and lipoproteins, muscle mass, and bone mineral density have been proposed, but few studies have directly addressed the impact of declining androgens on these parameters. In addition, the mechanisms responsible for the large decline in "bioavailable T", despite only modest decline in total serum T, have not been investigated. In a double blind placebo controlled crossover trial, men with screening T less than or equal to 3.5ng/ml will be given additional T and the effects will be studied on (a) parameters indicative of bone turnover, (b) serum lipids, lipoproteins, and lean body mass, (c) prostate size and urinary flow parameters, and (d) sex hormone levels and SHBG structure, binding affinity for androgens, and serum half life. If, as expected, modest T replacement leads to changes indicative of decreased bone turnover or resorption and/or increase in lean body mass, without serious changes to prostate size and serum lipids, a longer trial of T replacement will be done to examine effects on bone density and muscle mass and strength. Studies of Androgen Action Using a 5-Alpha Reductase Inhibitor: Evidence suggests that the permissive androgen in development of benign prostatic hyperplasia (BPH) is dihydrotestosterone (DHT), not T. Recently, a compound that inhibits the conversion of T to DHT (a 5-alpha reductase inhibitor) has been developed. The effect of this compound in the CNS and the subsequent control of gonadotropin secretion are not known. This study will investigate in rats, the ability of the compound to decrease brain levels of DHT and its ultimate effect on gonadotropin levels. This research will give important information about the contribution of DHT to steroid negative feedback regulation of LHRH secretion that could be applicable to man.

老年男性睾丸激素（T）替代的影响：许多 研究表明，随着正常男性的年龄，有一个逐渐 睾丸功能下降，包括中等减少 总血清T和“生物可利用T”的较大下降（t不绑定 到性激素结合球蛋白，SHBG）。 之间的关系 这种与年龄相关的雄激素水平和年龄相关的下降 生理参数的变化，例如血清脂质和 脂蛋白，肌肉质量和骨矿物质密度已经 提出的，但很少有研究直接解决了 这些参数下降的雄激素。 另外， 导致“生物利用T”大幅下降的机制， 尽管总血清t只有适中下降，但没有 调查。 在双盲安慰剂受控跨界试验中，男人 筛查t小于或等于3.5ng/ml将获得额外 t和效果将在（a）参数上研究 骨转换，（b）血清脂质，脂蛋白和瘦体重， （c）前列腺大小和尿流参数，以及（d）性激素 水平和SHBG结构，对雄激素的结合亲和力，以及 血清半衰期。 如果正如预期的那样，适度的替换会导致 变化表示骨转换或吸收减少 和/或瘦体重的增加，没有严重改变 前列腺尺寸和血清脂质，T替换的较长试验将 进行检查以检查对骨密度和肌肉质量的影响以及 力量。 使用5-α还原酶抑制剂对雄激素作用的研究： 有证据表明，开发的允许雄激素 良性前列腺增生（BPH）是二氢睾丸激素（DHT）， 最近不是T。 已经开发了DHT（5-α还原酶抑制剂）。 这 该化合物在中枢神经系统中的影响以及随后的控制 促性腺激素分泌尚不清楚。 这项研究将调查 在大鼠中，化合物降低大脑水平的能力 DHT及其对促性腺激素水平的最终影响。 这项研究 将提供有关DHT对的重要信息 LHRH分泌的类固醇负反馈调节 可能适用于人。