MECHANISMS UNDERLYING PHOTOPERIODIC REGULATION OF PITUITARY FSH AND LH RELEASE

在动物中表现出的最突出的年节律之一是 光周期依赖的季节性变化的生殖活动。虽然大部分 在理解生理机制方面已经取得了进展， 潜在的光周期控制繁殖在系统的 水平上，对细胞和分子事件知之甚少， 中枢神经系统和下丘脑-垂体轴， 在生殖活跃和不活跃之间的过渡 states.雄性西伯利亚仓鼠是一个有吸引力的模型， 机制研究有三个原因：1）明显的变化， 生殖神经内分泌功能可以在1-2天内诱导， 光刺激，2）卵泡刺激素（FSH）是选择性的 光刺激后合成和释放，和3）促性腺激素 在长光周期饲养的雄性中， 暴露于雌性，但这种诱导在暴露于 短光周期拟议项目的总体目标是 阐明了光致发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雌性， 最终影响垂体促性腺激素的释放。各种 实验技术（即，操纵激素和 通过输注外源性激素或用 激动剂或拮抗剂，检测mRNA的细胞内变化， 使用核糖核酸酶保护测定，定量rtPCR， 原位杂交、免疫细胞化学和放射免疫测定）将被 为实现这些目标。 预计拟议的研究将产生有关 将环境信息综合到 调节下丘脑-垂体-性腺轴的活动， 预期将导致更好地了解生育率， 不孕鉴于越来越多的证据表明，光周期和 化学感觉信号可以影响人类生殖， 研究也有望导致新的见解的基本 环境因素影响人类生殖的机制 因素

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.