EFFECT OF MELATONIN ON HUMAN CIRCADIAN RHYTHMS

褪黑激素对人体昼夜节律的影响

• 批准号: 2247410
• 负责人: ROBERT L SACK
• 金额: $ 18.98万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2247410
• 关键词: atenolol; beta adrenergic receptor; biological clocks; blindness; blood tests; circadian rhythms; drug administration rate /duration; gas chromatography; hormone metabolism; human subject; melatonin; pineal body; psychophysiology; radioimmunoassay; sleep

Melatonin is a hormone produced by the pineal gland at night that may be involved in the natural regulation of circadian rhythms. Animal studies have shown that exogenous melatonin administration can synchronize "free- running" circadian rhythms and can accelerate the rate of adaptation to a new rest/activity cycle. In studies currently in progress, we administered melatonin orally to five totally blind subjects with free-running endogenous melatonin rhythms in an attempt to entrain them to a 24-hour day. Although entrainment did not result, melatonin treatment produced large phase advances in the endogenous melatonin rhythms. These advances are much more robust than when melatonin is given to sighted people, possibly because the competing time cues from the light-dark cycle are not present in the blind subjects. In this project, we will evaluate the constraining effects of the light- dark cycle by giving melatonin to both blind and sighted subjects. We will define the parameters that produce the maximal phase-advancing effects in both groups by varying the timing, dose and duration of melatonin administration. We will attempt to enhance the phase-advancing effects of exogenous melatonin administration by suppressing endogenous melatonin production with the drug atenolol will test the effects of melatonin in sighted subjects who are adapting to an abrupt advance of their sleep-wake cycle (a laboratory model of shift work adaptation). We will evaluate the phase-advancing effects of exogenous melatonin administration by measuring its effect on the timing (phase) of endogenous melatonin production by the pineal gland. Phase will be assessed by obtaining serial blood samples and measuring plasma melatonin concentrations to determine the precise "onset" of active production. An RIA will be employed for efficiently processing most of the samples but critical values around the time of the melatonin onset will be verified with a highly specific gas chromatographic negative ion mass spectrometric assay. These studies may lead to the use of melatonin as a way to treat both blind and sighted patients with abnormal circadian rhythms.

褪黑激素是松果体在夜间产生的一种激素， 参与生理节奏的自然调节。 动物研究 已经表明外源褪黑激素给药可以同步“游离- 跑步”的昼夜节律，可以加快适应的速度， 新的休息/活动周期。 在目前正在进行的研究中，我们给予 褪黑激素口服5个完全失明的受试者， 内源性褪黑激素节律，试图将它们带入24小时 天 虽然夹带没有结果，褪黑激素治疗产生 内源性褪黑激素节律的大相位提前。 这些进步 比给视力正常的人服用褪黑激素时要强壮得多， 这可能是因为来自光暗周期的竞争时间线索 存在于盲人受试者中。 在这个项目中，我们将评估光的约束效果- 通过给盲人和视力正常的受试者服用褪黑激素来进行黑暗周期。 我们将 定义产生最大相位超前效应的参数， 通过改变褪黑素的时间、剂量和持续时间， 局 我们将尝试增强相位推进效应， 通过抑制内源性褪黑激素给予外源性褪黑激素 生产与药物阿替洛尔将测试褪黑激素的影响， 视力正常的受试者正在适应睡眠-觉醒的突然提前， 循环（轮班工作适应的实验室模型）。 我们将评估外源性褪黑激素的相位推进作用 通过测量其对内源性肿瘤的时间（阶段）的影响， 松果体产生褪黑激素。 阶段评估将由 获得系列血液样品并测量血浆褪黑激素 浓度以确定活性生产的精确“开始”。 一个 RIA将用于有效处理大多数样品， 将验证褪黑激素起效时间附近的临界值 用高特异性的气相色谱负离子质谱仪 比色法 这些研究可能会导致使用褪黑激素作为一种治疗方法 无论是盲人还是视力正常的病人都有异常的昼夜节律。