MECHANISMS UNDERLYING PHOTOPERIODIC REGULATION OF PITUITARY FSH AND LH RELEASE

在动物身上表达的最突出的年度节律之一是 生殖活动中与光周期相关的季节变化。虽然有很多 在理解生理机制方面取得了进展。 在系统的光周期繁殖控制的基础上 水平，对细胞和分子内的事件知之甚少 中枢神经系统和下丘脑-垂体轴 在繁殖活跃和不活跃之间的过渡是基础 各州。雄性西伯利亚仓鼠就是这样一个有吸引力的模型 机械论研究有三个原因：1)在 生殖神经内分泌功能可在1-2天内诱导 光刺激，2)卵泡刺激素(FSH)选择性地 光刺激后合成和释放，以及3)促性腺激素 在长时间的光周期下，雄性可以被诱导分泌 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 阐明形成光的早期细胞和分子事件 下丘脑促性腺激素释放激素(GnRH)升高的诱导 和脑下FSH含量，并确定光周期如何改变 处理传入信号以响应于暴露于 最终影响脑下垂体促性腺激素的释放。各种各样的 实验技术(即，荷尔蒙和 神经递质系统通过输注外源激素或用 激动剂或拮抗剂，检测细胞内mRNA和 蛋白质含量采用核糖核酸酶保护分析、定量RT-PCR、 原位杂交、免疫细胞化学和放射免疫分析)将 用来实现这些目标。 预计拟议的研究将提供有关 整合环境信息的基本机制 调节下丘脑-垂体-性腺轴的活动 有望使人们更好地理解生育和 不孕不育。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的生殖，建议 研究也有望带来对根本问题的新见解。 人类生殖受环境影响的机制 各种因素。

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.