CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

这个子项目是许多利用 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。我们还发现了一些物质的变化，这些物质反映了负能量平衡（抑制瘦素，胰岛素），并且可能参与哺乳期间的慢性摄食过多，这是一种类似于肥胖的情况。目前的研究是使用下丘脑外植体和电生理学来确定是否NPY，食欲素或黑色素浓集激素对GnRH神经元有直接的抑制作用。研究还将瘦素和胰岛素恢复到泌乳后水平，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。在大鼠中的研究结果形成了一个新的资助项目的基础，该项目研究控制恒河猴的食物摄入。

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.