NUTRITIONAL INFLUENCE ON HYPOTHAMALAMIC CONTROL

这项拟议研究的总体目标是确定血液是否- 携带的信号(胰岛素、葡萄糖、氨基酸、脂肪酸和 酮)直接作用于下丘脑组织来调节 下丘脑组织灌流过程中LHRH的释放。是这样的 这种作用可以解释临床潜在的病理生理学。 厌食症和运动相关女性的症状观察 生殖功能发生了改变。这一目标将是 通过使用独特的、定制设计的计算机来实现- 密歇根大学开发的受控灌流系统 密歇根州，并使用多传感器微型探头进行在线 监测组织的多单位电活动、温度 以及氧分压。该系统允许用户提供 确定的、但动态变化的营养素和 对培养细胞的刺激以及平衡氧分压和 降低中枢性缺氧和最大限度减少外周血流量 外植体中的氧毒性。下丘脑组织会 取自成熟的去卵巢雌性大鼠，放置在 灌流系统，并定期暴露在较高或较低的环境中 所需信号的浓度。特别是，尝试将 被用来确定对 下丘脑脉冲发生器通过监测以下各项 反应参数：(1)组织电活动(诱发 电位)在内侧基底区-视前区的多个位置进行测量 并检查下丘脑的周期性变化。 电活动频率，从一开始的过渡时间 频率到另一个和信号幅度(使用电位法)； 和(2)向周围媒体释放LHRH，量化为 放射免疫分析(RIA)。

The overall goal of the proposed study is to determine if blood- borne signals (insulin, glucose, amino-acids, fatty acids and ketones) act directly on hypothalamic tissue to modulate the release of LHRH In hypothalamic explants during perifusion. Such effect could explain the pathophysiology underlying clinical syndromes observed in anorexic and athletic women associated with altered reproductive function. This objective will be approached through use of a unique, custom-designed, computer- controlled perifusion system developed at The University of Michigan, and the use of a multi-sensor micro-probe for online monitoring of tissue's electrical multi-unit activity, temperature and oxygen tension. This system allows the user to provide a defined, yet dynamically-changing, pattern of nutrients and stimuli to cultured cells as well as balancing oxygen tension and flow rate to reduce central hypoxia and minimize peripheral oxygen toxicity in the explant. Hypothalamic tissue will be obtained from mature, ovariectomized female rats, placed in the perifusion system, and periodically exposed to higher or lower concentrations of the desired signal. In particular, attempts will be made to determine the effect on the oscillatory activity of the hypothalamic pulse generator by monitoring the following response parameters: (1) the tissue's electrical activity (evoked potentials) measured at multiple sites in the medial basal-preoptic area of the hypothalamus and examined for periodic changes in frequency of electrical activity, transition time from one frequency to another and signal amplitude (using potentiometry); and (2) LHRH release to the surrounding media, quantified by radioimmunoassay (RIA).