Melatonin Receptors: Localization and Regulation in Mammalian Brain
Melatonin Receptors: Localization and Regulation in Mammalian Brain
批准号:
8908542
负责人:
David Weaver
金额:
$13.95万
依托单位国家:
美国
项目类别:
Continuing Grant
财政年份:
1990
资助国家:
美国
项目状态:
已结题
起止时间:
1990-02-01 至 1992-07-31
中文摘要
褪黑素是一种由松果体产生和分泌的激素,已知在哺乳动物的生殖调节中具有重要作用。这种荷尔蒙还影响包括人类在内的许多物种的昼夜节律。通过昼夜节律系统调节褪黑激素的产生已经被广泛研究,松果体中的生化机制也是褪黑素生物合成所必需的。在了解褪黑素的作用方面仍然是一个主要的谜团,即确定其作用部位和作用机制。韦弗博士开发并验证了一种定量放射自显影方法,该方法使用碘标记的褪黑素来定位其在大脑中的作用部位。他将使用这项技术来表征中枢神经系统中的褪黑素结合部位,然后将特定神经元结构中结合活性的变化与各种生理条件联系起来。了解褪黑素的作用部位和机制具有广泛的意义,因为这种激素调节人类的昼夜节律,并可能有助于治疗与生物节律异常相关的疾病,如时差和抑郁症。此外,阐明褪黑激素调节季节性繁殖动物繁殖的机制可能揭示适用于家畜繁殖调节的一般机制。对褪黑素作用部位和机制的基础研究是迈向这些目标的必要的第一步。
英文摘要
Melatonin is a hormone produced and secreted by the pineal gland and known to have an important role in the regulation of mammalian reproduction. This hormone also influences circadian rhythmicity in a number of species, including humans. The regulation of melatonin production by the circadian timing system has been studied extensively as have the biochemical mechanisms in the pineal which are necessary for melatonin biosynthesis. The major enigma remaining in understanding the role of melatonin has been identification of its sites and mechanism of action. Dr. Weaver has developed and validated a quantitative autoradiographic method using an iodinated melatonin to localize its sites of action in the brain. He will use this technique to characterize the melatonin binding sites in the central nervous system and then correlate changes in binding activity within specific neuronal structures with various physiological conditions. Understanding the sites and mechanism of melatonin action has wide-ranging implications, as the hormone modulates circadian rhythmicity in humans and may be useful in treating conditions associated with abnormalities of biological rhythms, such as jet lag and depression. Furthermore, elucidating the mechanism by which melatonin regulates reproduction in animals that breed seasonally may reveal general mechanisms for the regulation of reproduction applicable to domestic farm animals. Basic research into the sites and mechanisms of melatonin action is a necessary first step towards these goals.
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