GLUCOSE METABOLISM EFFECTS ON REPRODUCTIVE BEHAVIOR

描述（改编自申请人的摘要）：能量可用性是 在所有控制繁殖的环境因素中最重要的。 减少食物摄入量，身体脂肪含量和增加运动量 对生育能力、排卵周期和性行为的巨大影响， 几乎所有被研究的雌性哺乳动物，包括女性。 总目标 拟议的研究是为了了解监测的感觉系统， 细胞能量可用性和抑制繁殖。 的具体目标 是为了更好地理解代谢刺激的本质， 他们的探测器的位置，以及从探测器到 控制生殖周期和行为的大脑区域。 全面掌握为 研究人员将检查以下大脑区域的影响： 各种代谢治疗对神经激活的影响（如通过FOS样 免疫反应性）在整个大脑中。 特别关注的领域将 检查其对葡萄糖药理学抑制剂的剂量反应 利用率 为了检查这些区域的功能意义， 或亚核，显示出神经激活的显着变化， 代谢抑制剂的影响，以观察这些抑制剂的缺乏是否 区域减弱或阻止代谢抑制剂对发情的影响 周期性（脊柱前凸和阴道分泌物）。 道的标准方法 追踪将用于确定尾脑的神经通路 干下丘脑神经元怀疑参与脉动GnRH 叙利亚仓鼠的分泌物。 另一组实验将检查 代谢信号的性质，通过比较不同代谢的能力， 脑室内输注底物以克服2-DG诱导的 乏情期 上述实验涉及已发表的技术， 在私家侦探的实验室里运行 最后的实验 建议将采取第一个茎对审查的实际 特定代谢脉冲LH分泌的神经内分泌效应和/或 GnRH神经元的神经激活。 了解代谢对行为的影响具有广泛的临床意义。 例如，不孕症总是与过度的身体 女性减肥 对上述所有现象的理解将 通过研究体重之间的联系， 营养、锻炼和生育能力。 然而，代谢的相互作用 燃料与神经系统的影响远远超出了 体重和生育能力之间的联系。 尽管我们几乎一无所知 代谢感觉的刺激和检测器，看来这种感觉 系统影响几乎每一种行为，包括性， 进食、攻击、母性行为和学习以及生理 确保热量平衡的过程。 此外，代谢效应 可能是行为和情绪障碍的基础， 老年痴呆症，焦虑症和抑郁症 拟议的实验将是一个 这是理解这些基础生物学的重要一步。 现象。

DESCRIPTION (Adapted from applicant's abstract): Energy availability is the most important of all environmental factors that control reproduction. Decreased food intake, body fat content, and increased exercise have dramatic effects on fertility, ovulatory cycles and sex behavior in virtually every female mammal studied, including women. The general goal of the proposed research is to understand the sensory system that monitors cellular energy availability and inhibits reproduction. The specific goals are to better understand the nature of metabolic stimuli, the anatomical location of their detectors, and the neural pathways from the detectors to brain areas controlling reproductive cycles and behavior. To get a picture of the brain areas involved, the investigators will examine the effects of various metabolic treatments on neural activation (as measured by FOS-like immunoreactivity) throughout the brain. Areas of particular interest will be examined for their dose response to pharmacological inhibitors of glucose utilization. To examine the functional significance of these areas, nuclei or subnuclei that show significant changes in neural activation in response to metabolic inhibitors will be lesioned to see whether the absence of these areas attenuate or prevent the effects of metabolic inhibitors on estrous cyclicity (lordosis and the vaginal discharge). Standard methods of tract tracing will be used to determine the neural pathways from the caudal brain stem to the hypothalamic neurons suspected to be involved in pulsatile GnRH secretion in Syrian hamsters. Another set of experiments will examine the nature of metabolic signals by comparing the ability of different metabolic substrates infused intracerebroventricularly to overcome 2-DG-induced anestrus. The above experiments involve techniques that are published and up-and-running in the PI's laboratory. The last experiments in this proposal will take the first stems toward examining the actual neuroendocrine effects of specific metabolic pulsatile LH secretion and/or neural activation in GnRH neurons. Understanding metabolic effects on behavior has broad clinical significance. For example, infertility is consistently associated with excessive body weight loss in women. An understanding of all of the above phenomena will be facilitated by research focused on the links among body weight, nutrition, exercise and fertility. However, the interaction of metabolic fuels with the nervous system has implications that reach far beyond the link between body weight and fertility. Although we know almost nothing of the stimuli and detectors for metabolic sense, it appears that this sensory system influences virtually every category of behavior including sex, eating, aggression, maternal behavior and learning and the physiological processes that insure caloric homeostasis. In addition, metabolic effects on the nervous system might underlie behavioral and mood disorders such as Alzheimer, anxiety and depression. The proposed experiments will be an important step toward understanding the basic biology that underlies these phenomena.