CONTROL OF GONADOTROPIN SECRETION DURING LACTATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。利用电生理技术，我们发现NPY对GnRH神经元有直接的抑制作用，这种抑制作用在哺乳期显著增强。如果被抑制的瘦素和/或胰岛素水平恢复到哺乳期后的正常水平，则对哺乳期的过度吞噬或抑制的黄体生成素分泌没有影响。这些结果表明，哺乳能量负平衡不是高噬或抑制GnRH/Lh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。这些研究的结果构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. 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.