NEUROENDOCRINOLOGY OF PUBERTY

总的目标是了解雌性如何决定何时 已经达到了开始青春期的大小，为什么在营养不良的性行为 没有达到成熟。 在这方面，我们想知道， 发育中的大脑监测生理大小和健康， 促性腺激素的分泌，启动第一个生殖周期。 我们的研究将集中在调节模式的机制， 促黄体生成激素（LH）分泌，因为增加的频率 LH的间歇性放电乘以青春期的开始。 的具体目标 建议的研究是：1）确定是否降低频率或 促性腺激素释放激素分泌的幅度是促性腺激素功能减退的原因， 营养诱导的生长迟缓，2）定义血液传播信号 其将关于代谢状态的信息与控制代谢的系统相关联。 脉冲LH分泌的频率，以及3）确定脑机制 通过营养和生长相关信号调节LH分泌。 将使用几种实验方法和方法来实现 我们的目标 我们开发了一个模型系统， 无卵巢的生长受限羔羊，其特征是LH非常缓慢 脉搏 LH分泌的调节机制对变化非常敏感 在营养水平上。 自由采食可快速增加（2-7 天）的LH分泌频率，并随后减少 饲料水平，LH脉冲频率同样迅速下降。 以确定 如果LH脉冲频率的变化与饮食的改变有关， 我们的模型反映了振幅或频率的变化， 垂体门脉循环中GnRH的特征将在于： 与外周循环中LH相关。 为了定义血液- 与控制GnRH的机制沟通的信号 分泌，葡萄糖和氨基酸的组合将被注入我们的 模型;将使用各种类型的肠外营养来确定是否 能源本身就是一个重要的信号。 肾上腺轴的活动将 也要检查。 将采用两种实验方法进行研究 营养不良状态下限制LH分泌的中枢机制。 首先，将使用药理学方法研究是否 内源性阿片和/或肾上腺素能机制抑制脉动LH 限制饮食羔羊的分泌物。 其次，免疫细胞化学 将在限制饮食羔羊中进行GnRH神经元分析， 恢复自由采食的羔羊。 这将决定是否 营养不良和再摄取改变了GnRH的形态和数量 免疫反应神经元 这种结合的方法将揭示是否 慢性营养不良引起的低促性腺激素状态是由于 GnRH合成减少，因此GnRH的可用性有限，或 对GnRH分泌和降解的主动抑制。 这个项目的结果与对青春期的理解有关， 更广泛地说，也适用于其他生理状态， 由大脑监控，以确定是否应该开始或 树立政治意识

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.