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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这些研究的重点是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)神经元的特定代谢信号或传入神经通路的身份仍不清楚，GnRH神经元是调节生殖的中央下丘脑系统。该项目的一个关键假设是，抑制Kispeptin信号是抑制GnRH的主要因素。虽然人们普遍认为，低血症症是连接能量平衡和抑制GnRH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Kispeptin或GnRH在哺乳或热量限制中的抑制作用。因此，低肽血症似乎不是导致生殖功能抑制的主要代谢因素。我们的假设是，脑干系统，如葡萄糖感觉神经元，可能是有关代谢信号的信息传递到Kispeptin神经元的场所。本项目的重点是两个假设：1)在负能量平衡状态下，在GnRH细胞体部位以及神经纤维和终末位置对Kispeptin信号的抑制是其抑制的主要成分；2)脑干系统作为代谢信号的整合部位，提供负责在负能量平衡状态下抑制Kisspeptin的传入信号。这些研究将确定调控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。