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.

动物中表达的最突出的年度节奏之一是 依赖于生殖活性的季节性变化。虽然很多 在理解生理机制方面取得了进展 在系统的繁殖的光周期控制的基础 水平，关于细胞和分子事件的了解很少 中枢神经系统和下丘脑 - 垂体轴 是生殖活性和非活性之间的过渡的基础 国家。西伯利亚男性仓鼠是这样的有吸引力的模型 机械研究的三个原因：1）明显变化 可以在1-2天内诱导生殖神经内分泌功能 光刺激，2）卵泡刺激激素（FSH）是选择性的 光刺激后合成并释放，3）促性腺激素 可以在长期光周期中诱导分泌的雄性 暴露于女性，但这种诱导被抑制 短光周期。拟议项目的总体目标是 阐明构成光学基础的早期细胞和分子事件 诱导下丘脑性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于对女性的暴露 最终影响垂体性促性腺激素释放。各种各样 实验技术（即激素和激素的操纵 神经递质系统通过输注外源激素或处理 激动剂或拮抗剂，检测mRNA和 使用核糖核酸酶保护测定的蛋白质含量，定量RTPCR， 原位杂交，免疫细胞化学和放射免疫测定）将是 用于实现这些目标。 预计拟议的研究将产生有关 将环境信息集成到的基本机制 调节下丘脑 - 垂体 - 基达轴的活性，为 预计会提高人们对生育能力和 不育。鉴于越来越多的证据表明光周期和 化学感信号会影响人类的繁殖 预计研究还会导致对基本的新见解 人类繁殖可以受到环境影响的机制 因素。