NEUROENDOCRINOLOGY OF PUBERTY

总体目标是了解雌性是如何决定何时 已经达到了开始青春期的体型，为什么在营养不良的情况下 成熟是没有达到的。在这方面，我们想知道 发育中的大脑监测生理尺寸和幸福感，以增加 启动第一个生殖周期的促性腺激素的分泌。 我们的研究将集中在调节模式的机制上 促黄体生成素(LH)分泌，因为 黄体生成素的间歇性分泌是青春期开始的时间。的具体目标 建议的研究是：1)确定频率降低或 促性腺激素释放激素分泌的幅度是促性腺激素分泌减少的原因。 营养导致的生长迟缓，2)定义血液传播的信号 将有关新陈代谢状态的信息与控制 脉动性黄体生成素分泌的频率，以及3)确定大脑机制 通过营养和生长相关信号调节黄体生成素的分泌。 将使用几种实验方法和方法来实现 我们的目标。我们已经开发了一个模型系统，营养 没有卵巢的生长受限的羔羊，其特点是促黄体生成素非常缓慢 脉搏。黄体生成素的分泌机制对变化非常敏感。 在营养水平上。自由采食会产生快速增长(2-7 天)黄体生成素分泌频率增加，随后减少 饲喂水平，黄体生成素脉冲频率同样迅速下降。要确定 如果黄体生成素脉搏频率的变化与饮食的改变有关 我们的模型反映了幅度或频率、模式和电平的变化 垂体门静脉循环中的GnRH的特征将是 与外周循环中促黄体生成素水平的关系。为了定义血液- 与GnRH调控机制通信的承载信号 分泌物，葡萄糖和氨基酸的组合将注入我们的 模型；将使用各种类型的肠外营养来确定 能源本身就是一个重要的信号。肾上腺轴的活动将 也要接受检查。将采用两种实验方法进行研究。 营养不良状态下限制黄体生成素分泌的中枢机制。 首先，将使用药理学方法来调查是否 内源性阿片和/或5-羟色胺能机制抑制搏动性黄体生成素 限制饮食的羔羊的分泌物。第二，一种免疫细胞化学物质 分析GnRH神经元将在限制饮食的羔羊和 在羔羊恢复自由饮食的情况下。这将决定是否 营养不良和营养状况改变促性腺激素释放激素的形态和数量 免疫反应神经元。这种结合的方法将揭示出 慢性营养不良所致的低促性腺激素状态 GnRH合成减少，因此GnRH的可获得性有限，或从 主动抑制促性腺激素释放激素的分泌和降解。 这个项目的结果与理解青春期有关， 更广泛地说，与其他生理状态有关，在这些状态中，体型和幸福感 由大脑监测，以确定是否应该开始生育 维护好了。

The overall objective is to understand how the female determines when she has achieved a size to begin puberty and why during poor nutrition sexual maturity is not attained. In this regard, we wish to know how the developing brain monitors physiologic size and well-being to increase the secretion of gonadotropins which initiate the first reproductive cycle. Our studies will concentrate on mechanisms regulating the pattern of luteinizing hormone (LH) secretion, since an increase in frequency of episodic discharges of LH times the onset of puberty. The specific aims of the proposed research are: 1) to determine if a reduced frequency or amplitude of GnRH secretion is responsible for hypogonadotropism during nutritionally induced growth retardation, 2) to define blood-borne signals which relate information about metabolic state to the system governing the frequency of pulsatile LH secretion, and 3) to determine brain mechanisms modulating LH secretion by nutritional and growth-related signals. Several experimental approaches and methodologies will be used to attain our objectives. We have developed a model system, the nutritionally growth-limited lamb without ovaries, which is characterized by very slow LH pulses. The mechanism governing LH secretion is very sensitive to changes in level of nutrition. Ad libitum feeding produces a rapid increase (2-7 days) in frequency of LH secretion, and following subsequent reduction of feed level, an equally rapid decrease in LH pulse frequency. To determine if the changes in LH pulse frequency associated with alteration in diet in our model reflect changes in amplitude or frequency, the pattern and level of GnRH in the pituitary portal circulation will be characterized in relation to that for LH in the peripheral circulation. To define blood- borne signals which communicate with the mechanism governing GnRH secretion, combinations of glucose and amino acids will be infused into our model; various types of parenteral nutrition will be used to determine if energy alone is an important signal. The activity of the adrenal axis will also be examined. Two experimental approaches will be adopted to study central mechanisms limiting LH secretion in the undernourished state. Firstly, a pharmacologic approach will be used to investigate whether endogenous opioid and/or serotoninergic mechanisms inhibit pulsatile LH secretion in the restricted-diet lamb. Secondly, an immunocytochemical analysis of GnRH neurons will be carried out in restricted-diet lambs and in lambs returned to ad libitum diet. This will determine whether undernutrition and realimentation alter the morphology and number of GnRH immunoreactive neurons. This combined approach will reveal whether the hypogonadotropic state induced by chronic undernutrition results from a decrease in GnRH synthesis and, thus, limited availability of GnRH, or from an active inhibition of GnRH secretion and degradation. The results of this project have relevance to the understanding of puberty, and more broadly, to other physiologic states in which size and well-being are monitored by the brain to determine if fertility should begin or be maintained.