CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。哺乳的特点是由于促性腺激素释放激素(GnRH)的抑制而抑制生殖周期，过度吞噬和因产奶而导致的能量负平衡。这一建议的中心假设是，GnRH/LH分泌的抑制是由于哺乳导致调节食物摄取和能量平衡的下丘脑神经系统的改变。我们最近的研究证实，参与调节食物摄入/能量平衡的几个下丘脑神经肽促食欲素系统(NPY、增食欲素、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，通过这个框架，表明食物摄入/能量平衡变化的信号可以直接传递到GnRH神经元。我们还发现，一些反映负能量平衡的物质(受抑制的瘦素、胰岛素)发生了变化，很可能与哺乳期的慢性吞噬症有关，这是一种类似肥胖的情况。目前的研究是利用下丘脑外植体和电生理学来确定NPY、增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期后的水平，并确定对下丘脑神经肽喂养系统和恢复GnRH/LH分泌的影响。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一系列情况(营养不良、神经性厌食症、暴食症和运动性闭经)提供了一个生理模型，这些条件涉及与能量平衡变化相关的生殖功能抑制。在老鼠身上的研究结果形成了一个新的资助项目的基础，该项目研究恒河猴的食物摄入控制。

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.