MATURATION OF PITUITARY RESPONSES TO GNRH IN HUMANS

本提案的总体目标是增进我们对 促性腺激素分泌调节的变化和推测的 GnRH分泌的变化，在人类性成熟和整个 月经周期 假设GnRH脉冲频率可能起作用， 调节作用，在人类性成熟和整个月经 周期将以几种方式进行审查。 具体而言，我们计划1） 详细描述促性腺激素分泌调节的变化 发生在儿童中后期和青春期早期之间; 2）确定 改变GnRH脉冲频率对大鼠促性腺激素分泌的影响 正常和性腺功能减退的成年人;和3）确定机制 导致卵泡期FSH/LH比值升高， 月经周期 我们实现这些目标的主要方法包括 a）以不同的浓度脉冲静脉内施用合成GnRH， 频率，但剂量模拟垂体门静脉浓度; B） 阿片受体阻滞剂，探讨促性腺激素的作用机制 儿童期的抑制; c）评估反馈是否影响 青春期中期的雌二醇或睾酮浓度 对青春期早期儿童睡眠-觉醒周期的影响;以及d）评估 是否给予雌二醇和孕酮以模拟黄体功能 周期的第一阶段可以逆转血清FSH/LH比值。 在 除了更好地了解生殖生理学，这些 研究应提供合理的治疗方案的基础， 未来

The overall aim of this proposal is to increase our understanding of the changes in the regulation of gonadotropin secretion and the presumed changes in GnRH secretion, during human sexual maturation and throughout the menstrual cycle. The hypothesis that GnRH pulse frequency may play a regulatory role in human sexual maturation and throughout the menstrual cycle will be examined in several ways. Specifically, we plan 1) to characterize in detail changes in the regulation of gonodotropin secretion which occur between mid-late childhood and early puberty; 2) to determine the effects of changing GnRH pulse frequency on gonadotropin secretion in normal and hypogonadal adults; and 3) to determine the mechanisms responsible for the increased FSH/LH ratio during the follicular phase of the menstrual cycle. Our major approaches to these objectives will include a) the pulsatile i.v. administration of synthetic GnRH at varying frequencies but at dosages which mimic pituitary portal concentrations; b) opiate receptor blockade to investigate the mechanisms of gonadotropin inhibition during childhood; c) assessment of whether the feedback effects of mid-pubertal concentrations of estradiol or testosterone are dependent on the sleep-wake cycle in early pubertal children; and d) assessment of whether administration of estradiol and progesterone to mimic the luteal phase of the cycle can effect a reversal in the serum FSH/LH ratio. In addition to a better understanding of reproductive physiology, these studies should provide the basis for rational therapeutic regimens in the future.