CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

哺乳期间促性腺激素分泌的控制

• 批准号: 8357727
• 负责人: M. SUSAN SMITH
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357727
• 关键词: Brain Stem; Caloric Restriction; Fertility; Funding; Glucose; Gonadotropin Hormone Releasing Hormone; Gonadotropins; Grant; Hypothalamic structure; Lactation; Lead; Leptin; Link; Metabolic; National Center for Research Resources; Nerve Fibers; Neural Pathways; Neurons; Pathway interactions; Physiological; Primates; Principal Investigator; Reproduction; Research; Research Infrastructure; Resources; Signal Transduction; Site; Source; System; United States National Institutes of Health; cost; energy balance; kisspeptin; neuronal cell body; reproductive function

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. These studies focus on states of negative energy balance that are associated with a suppression of reproductive function. The identity of the specific metabolic signals or afferent neural pathways that convey information about energy balance to gonadotropin-releasing hormone (GnRH) neurons, the central hypothalamic system regulating reproduction, remains elusive. A key hypothesis of this project is that suppression of kisspeptin signaling is the primary factor in the inhibition of GnRH. Although it is a widely held view that hypoleptinemia is the critical factor linking energy balance and suppressed GnRH, our recent studies demonstrate that restoring leptin to normal physiological levels does not reverse the inhibition of kisspeptin or GnRH in either lactation or caloric restriction. Thus, hypoleptinemia does not appear to be the primary metabolic factor responsible for the suppression of reproductive function. Our hypothesis is that brainstem systems, such as glucose sensing neurons, may be the site where information about metabolic signals is relayed to kisspeptin neurons. This project focuses on two hypotheses: 1) Suppression of kisspeptin signaling at the site of GnRH cell bodies and at nerve fibers and terminals are primary components in its inhibition during states of negative energy balance, and 2) Brainstem systems serve as a site of integration of metabolic signals and provide the afferent signals that are responsible for the suppression of kisspeptin during negative energy balance. These studies will identify new pathways that regulate control GnRH neurons and could lead to new treatments for restoring fertility in states of negative energy balance.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 这些研究重点关注与生殖功能抑制相关的负能量平衡状态。将能量平衡信息传递给促性腺激素释放激素（GnRH）神经元（调节生殖的中枢下丘脑系统）的特定代谢信号或传入神经通路的身份仍然难以捉摸。该项目的一个关键假设是 Kisspeptin 信号传导的抑制是抑制 GnRH 的主要因素。 尽管人们普遍认为低瘦素血症是联系能量平衡和 GnRH 抑制的关键因素，但我们最近的研究表明，将瘦素恢复到正常生理水平并不能逆转哺乳期或热量限制中 Kisspeptin 或 GnRH 的抑制。因此，低瘦素血症似乎不是抑制生殖功能的主要代谢因素。我们的假设是，脑干系统，例如葡萄糖感应神经元，可能是将代谢信号信息传递给 Kisspeptin 神经元的部位。该项目重点关注两个假设：1) GnRH 细胞体部位以及神经纤维和末梢对 Kisspeptin 信号传导的抑制是负能量平衡状态下其抑制的主要组成部分，2) 脑干系统作为代谢信号整合的部位，并提供负责在负能量平衡期间抑制 Kisspeptin 的传入信号。这些研究将确定调节 GnRH 神经元的新途径，并可能导致在负能量平衡状态下恢复生育能力的新疗法。