CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

哺乳期间促性腺激素分泌的控制

• 批准号: 8173173
• 负责人: M. SUSAN SMITH
• 金额: $ 15.22万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173173
• 关键词: Amenorrhea; Anorexia Nervosa; Computer Retrieval of Information on Scientific Projects Database; Controlled Study; Eating; Exercise; Funding; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Grant; Hyperphagia; Hypothalamic structure; Institution; Insulin; Lactation; Leptin; Macaca mulatta; Malnutrition; Milk; Neurons; Neuropeptides; Periodicity; Physiological; Production; Research; Research Personnel; Resources; Signal Transduction; Source; Study models; System; Techniques; United States National Institutes of Health; Woman; base; energy balance; hypocretin; inhibitory neuron; melanin-concentrating hormone; relating to nervous system; reproductive; reproductive function

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. Using electrophysiological techniques, we showed that NPY has direct inhibitory effects on GnRH neurons; these inhibitory effects are greatly increased during lactation. If the suppressed levels of leptin and/or insulin were restored to normal postlactation levels , there is no effect on the hyperphagia or the suppressed LH secretion during lactation. These results suggest that the negative energy balance of lactation is not a prerequisite for the hyperphagia or the suppression of GnRH/LH. 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 formed the basis of a new funded project to study control of food intake in the rhesus monkey.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 泌乳的特征在于由于促性腺激素释放激素（GnRH）的抑制而导致的生殖周期的抑制、由于产奶而导致的过度摄食和负能量平衡。这一建议的中心假设是，GnRH/LH分泌的抑制是由于哺乳引起的下丘脑神经系统的改变，调节食物摄入和能量平衡。我们最近的研究表明，参与调节食物摄入/能量平衡的几种下丘脑神经肽食欲系统（NPY，食欲素，黑色素浓缩激素）与GnRH神经元直接联系，从而提供了一个神经解剖学框架，通过该框架，指示食物摄入/能量平衡变化的信号可以直接传递到GnRH神经元。使用电生理技术，我们发现，NPY对GnRH神经元有直接的抑制作用，这些抑制作用在哺乳期大大增加。 如果抑制的瘦素和/或胰岛素水平恢复到正常泌乳后水平，则对泌乳期间的摄食过多或LH分泌抑制没有影响。 这些结果表明，哺乳期的负能量平衡不是食欲过盛或GnRH/LH抑制的先决条件。哺乳期间生殖功能和能量平衡之间的相互作用为研究妇女的一些状况（营养不良、神经性厌食症、贪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有关的生殖功能抑制。这些研究结果构成了一个新的资助项目的基础，该项目旨在研究恒河猴的食物摄入控制。