CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

哺乳期间促性腺激素分泌的控制

• 批准号: 7958401
• 负责人: M. SUSAN SMITH
• 金额: $ 8.03万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958401
• 关键词: Amenorrhea; Anorexia Nervosa; Chronic; Computer Retrieval of Information on Scientific Projects Database; Controlled Study; Eating; Electrophysiology (science); Exercise; Funding; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Grant; Hyperphagia; Hypothalamic structure; Institution; Insulin; Lactation; Leptin; Macaca mulatta; Malnutrition; Milk; Neurons; Neuropeptides; Obesity; Periodicity; Physiological; Primates; Production; Rattus; Research; Research Personnel; Resources; Signal Transduction; Source; Study models; System; United States National Institutes of Health; Woman; base; energy balance; feeding; hypocretin; melanin-concentrating hormone; relating to nervous system; reproductive; reproductive function; restoration

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lactation is characterized by an inhibition of reproductive cyclicity due to a suppression of gonadotropin releasing hormone (GnRH), excessive hyperphagia and negative energy balance due to milk production. The central hypothesis of this proposal is that suppression of GnRH/LH secretion is due to suckling-induced alterations in hypothalamic neural systems that regulate food intake and energy balance. Our studies have recently established that several hypothalamic neuropeptide orexigenic systems involved in regulating food intake/energy balance (NPY, orexin, melanin concentrating hormone) make direct connections with GnRH neurons, thus providing a neuroanatomical framework by which signals denoting changes in food intake/energy balance can be directly transmitted to GnRH neurons. We have also found changes in a number of substances that reflect the negative energy balance (suppressed leptin, insulin) and are likely to be involved in the chronic hyperphagia during lactation, a condition similar to obesity. Current studies are using hypothalamic explants and electrophysiology to determine if NPY, orexin or melanin concentrating hormone have direct inhibitory effects on GnRH neurons. Studies are also restoring leptin and insulin to postlactation levels and determining the effects on hypothalamic neuropeptide feeding systems and on restoration of GnRH/LH secretion. The interaction between reproductive function and energy balance during lactation provides a physiological model for studying a number of conditions in women (undernutrition, anorexia nervosa, bulimia and exercise-induced amenorrhea) that involve a suppression of reproductive function associated with changes in energy balance. The results of the studies in the rat formed the basis of a new funded project to study control of food intake in the rhesus monkey.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 哺乳期的特点是由于促性腺激素释放激素 (GnRH) 抑制而抑制生殖周期、过度进食以及由于产奶而导致能量负平衡。该提议的中心假设是，GnRH/LH 分泌的抑制是由于哺乳引起的调节食物摄入和能量平衡的下丘脑神经系统的改变所致。我们的研究最近证实，几种参与调节食物摄入/能量平衡的下丘脑神经肽促食欲系统（NPY、食欲素、黑色素浓缩激素）与 GnRH 神经元直接连接，从而提供了一个神经解剖学框架，通过该框架发出指示食物摄入/能量变化的信号平衡可直接传递至 GnRH 神经元。我们还发现许多反映能量负平衡的物质（瘦素、胰岛素受到抑制）发生变化，并且可能与哺乳期慢性食欲过多有关，这种情况类似于肥胖。目前的研究正在使用下丘脑外植体和电生理学来确定 NPY、食欲素或黑色素浓缩激素是否对 GnRH 神经元有直接抑制作用。研究还将瘦素和胰岛素恢复到哺乳后水平，并确定对下丘脑神经肽喂养系统和 GnRH/LH 分泌恢复的影响。哺乳期间生殖功能和能量平衡之间的相互作用为研究女性的许多状况（营养不良、神经性厌食症、暴食症和运动引起的闭经）提供了一个生理模型，这些状况涉及与能量平衡变化相关的生殖功能抑制。对大鼠的研究结果构成了一项新资助项目的基础，该项目旨在研究恒河猴食物摄入的控制。