NUTRITIONAL INFLUENCE ON HYPOTHALAMIC CONTROL

这项研究的总体目标是确定血液- 所携带的信号（胰岛素、葡萄糖、氨基酸、脂肪酸和 酮）直接作用于下丘脑组织以调节 下丘脑移植物灌流过程中LHRH的释放。 等 作用可以解释临床基础的病理生理 在女性运动员和运动员中观察到的综合征 生殖功能改变 这一目标将是 通过使用一个独特的，定制设计的，计算机- 控制灌注系统开发的大学 密歇根州，并使用多传感器的微型探针在线 监测组织的电多单元活动、温度 和氧分压。 该系统允许用户提供 定义，但动态变化，营养模式， 刺激培养的细胞以及平衡氧张力， 流速，以减少中枢缺氧，并最大限度地减少外周 取出物中的氧毒性。 下丘脑组织将 从切除卵巢的成熟雌性大鼠中获得，置于 灌注系统，并定期暴露于更高或更低 所需信号的浓度。 特别是， 确定对振荡活动的影响， 下丘脑脉冲发生器通过监测以下 响应参数：（1）组织的电活动（诱发的 在内侧基底-视前区的多个部位测量 下丘脑的区域，并检查下丘脑的周期性变化， 电活动的频率，从一个 频率到另一个和信号幅度（使用电位法）; 和（2）LHRH释放到周围介质中，通过 放射免疫分析法（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).