MECHANISMS UNDERLYING PHOTOPERIODIC REGULATION OF PITUITARY FSH AND LH RELEASE

垂体 FSH 和 LH 释放的光周期调节机制

• 批准号: 6410465
• 负责人: FRED W TUREK
• 金额: $ 17.7万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-15 至 2001-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6410465
• 关键词: RNase protection assay; biological signal transduction; central neural pathway /tract; circadian rhythms; follicle stimulating hormone; glutamates; gonadotropin releasing factor; hamsters; hormone regulation /control mechanism; hypothalamic pituitary axis; in situ hybridization; inhibin; luteinizing hormone; melatonin; neural information processing; neuroendocrine system; peptide hormone biosynthesis; pheromone; photostimulus; pituitary gonadal axis; polymerase chain reaction; reproduction; reproductive development; secretion; transcription factor

One of the most prominent annual rhythms expressed in animals is the photoperiod-dependent seasonal change in reproductive activity. While much progress has been made in understanding the physiological mechanisms underlying the photoperiodic control of reproduction at the system's level, very little is known about the cellular and molecular events within the central nervous system and the hypothalamic-pituitary axis that underlie the transition between the reproductively active and inactive states. The male Siberian hamster is an attractive model for such mechanistic studies for three reasons: 1) pronounced changes in reproductive neuroendocrine function can be induced within 1-2 days of photostimulation, 2) follicle stimulating hormone (FSH) is selectively synthesized and released following photostimulation, and 3) gonadotropin secretion can be induced in males housed in long photoperiod following exposure to a female, but this induction is inhibited in males exposed to short photoperiods. The overall objectives of the proposed project are to elucidate the early cellular and molecular events that underlie the photic induction of increased hypothalamic gonadotropin releasing hormone (GnRH) and pituitary FSH content and to determine how the photoperiod alters the processing of afferent signals in response to exposure to a female that ultimately influences pituitary gonadotropin release. A variety of experimental techniques (i.e., manipulation of hormone and neurotransmitter system by infusion of exogenous hormone or treatment with agonists or antagonists, detection of intracellular changes in mRNA and protein content using ribonuclease protection assays, quantitative rtPCR, in situ hybridization, immunocytochemistry, and radioimmunoassay) will be employed to achieve these objectives. The proposed studies are expected to yield new information about the fundamental mechanisms by which environmental information is integrated to regulate the activity of the hypothalamic-pituitary-gonadal axis and are expected to lead to an improved understanding of fertility and infertility. In view of the increasing evidence that both photoperiod and chemosensory signals can influence human reproduction, the proposed studies are also expected to lead to new insights into the fundamental mechanisms by which human reproduction can be influenced by environmental factors.

动物表现出的最突出的年度节律之一是 生殖活动的光周期依赖性季节变化。虽然很多 在理解生理机制方面取得了进展 系统繁殖的光周期控制的基础 水平上，人们对其中的细胞和分子事件知之甚少。 中枢神经系统和下丘脑-垂体轴 是生殖活跃和不活跃之间转变的基础 州。雄性西伯利亚仓鼠是此类动物的有吸引力的模型 机制研究的三个原因：1）显着的变化 1-2天内即可诱导生殖神经内分泌功能 光刺激，2）选择性地促卵泡激素（FSH） 光刺激后合成并释放，3) 促性腺激素 雄性在长光周期饲养后可诱导分泌 暴露于女性，但这种诱导在暴露于女性的男性中受到抑制 光周期短。拟议项目的总体目标是 阐明光的早期细胞和分子事件 诱导下丘脑促性腺激素释放激素 (GnRH) 增加 和垂体 FSH 含量，并确定光周期如何改变 处理传入信号以响应暴露于女性的情况 最终影响垂体促性腺激素的释放。各种 实验技术（即激素和 通过输注外源激素或治疗来改善神经递质系统 激动剂或拮抗剂，检测细胞内 mRNA 的变化和 使用核糖核酸酶保护测定、定量 rtPCR 测定蛋白质含量， 原位杂交、免疫细胞化学和放射免疫分析） 受雇来实现这些目标。 拟议的研究预计将产生有关 环境信息整合的基本机制 调节下丘脑-垂体-性腺轴的活动， 预计将提高对生育力和 不孕症。鉴于越来越多的证据表明光周期和 化学感应信号可以影响人类生殖，建议 研究也有望带来对基本原理的新见解 环境影响人类繁殖的机制 因素。