NEURAL MECHANISMS MEDIATING SEASONAL REPRODUCTIVE CYCLES

虽然我们知道了很多关于白昼长度对 哺乳动物血液循环水平和性腺功能的季节性变化， 关于白天长度对神经的影响，我们知之甚少。 调节生殖系统季节性变化的机制。 最近有研究表明，雄性西伯利亚仓鼠(Photopus) 从短天数转换为长天数)表现出增加了 含有可检测水平的下丘脑神经元的数量 染毒后促性腺激素释放激素(GnRH)mRNA的表达 漫长的一天。随后，含有GnRH mRNA的细胞数量恢复 降至基线(短日照)水平。基因的这种快速和短暂的变化 Expression定义了一个时间窗口，在此窗口中可以阐明早期的 发生在大脑中的细胞、神经化学和分子变化 在从光抑制的神经内分泌的最初转变过程中 系统进入光刺激状态。这份提案描述了三套 旨在描述和阐明这些机制的实验。这个 本项目的具体目标是检验以下假设：1) 光刺激导致GnRH从下丘脑迅速释放，并 合成随后被刺激返回下丘脑GnRH含量 到基线水平，2)原癌基因c-fos的表达 作为参与照片早期阶段的GnRH神经元的标记- 对下丘脑-垂体-性腺轴(HPG)的诱导刺激，以及 可能与下丘脑细胞中含有GnRH mRNA的增加有关， GnRH基因表达的快速增加依赖于变化 松果体分泌褪黑激素的模式。结果是 这些研究有望为生理学、 HPG季节变化的细胞和分子机制 轴心。此外，这些结果可能会为我们提供对基本的 动物神经内分泌系统可塑性的调节机制， 包括人类。

Although a great deal is known about the effects of day length on seasonal changes in circulating levels and gonadal function in mammals, much less is known about the effects of day length on the neural mechanisms which mediate seasonal changes in the reproductive system. Recently it has been demonstrated that male Siberian hamsters (Phodopus sungorus) transferred from short to long days exhibit an increase in the number of hypothalamic neurons containing detectable levels of gonadotrophin-releasing hormone (GnRH) mRNA after exposure to the first long day. Subsequently, the number of GnRH mRNA-containing cells returns to baseline (short-day) levels. This rapid and transient change in gene expression defines a window of time in which to elucidate the early cellular, neurochemical, and molecular changes that occur in the brain during the initial transition from a photically inhibited neuroendocrine system to a photostimulated state. This proposal describes three sets of experiments designed to characterize and elucidate these mechanisms. The specific aims of this project are to test the following hypotheses: 1) photostimulation causes a rapid release of GnRH from the hypothalamus and synthesis is subsequently stimulated to return hypothalamic GnRH content to baseline levels, 2) the expression the proto-oncogene c-fos can be used as a marker of GnRH neurons involved in the early stages of photo- induced stimulation of the hypothalamo-pituitary-gonadal (HPG) axis, and may be related to increases in hypothalamic cells containing GnRH mRNA, an 3) rapid increases in GnRH gene expression are dependent upon changes in patterns of melatonin secretion from the pineal gland. The results of these studies are expected to shed new light on the physiological, cellular, and molecular mechanisms underlying seasonal changes in the HPG axis. Moreover, the results may provide important insight into the basic mechanisms mediating plasticity in neuroendocrine systems in animals, including humans.