OVARIAN HORMONE REGULATION OF LHRH BIOSYNTHESIS

这项研究的长期目标是确定 雌激素(E)和孕酮(P)的神经内分泌机制 控制黄体生成素的排卵前高峰释放。 尽管LHRH神经元不集中E或P，但它们充当最终的 多个神经递质系统翻译的共同途径 将来自卵巢的信息转化为调节黄体生成素释放的信号。这个 卵巢激素对LHRH释放的调节作用已被广泛研究； 然而，E和P对LHRH的影响知之甚少 生物合成。这些信息以前很大程度上是无法获得的 因为LHRH基因还没有被描述，而LHRH的结构 前荷尔蒙是未知的。本研究将使用新开发的 针对LHRH前激素和LHRH mRNA特异性的方法和探针 确定LHRH生物合成是否在 左旋波释放。工作假说是卵巢激素 刺激促黄体生成素释放激素在黄体生成素高峰前从头合成 高峰期高分泌伴随着LHRH基因的升高 抄写。为检验这一假设而提出的研究也将 提供有关LHRH转录之间的关系的信息， 稳态LHRH mRNA水平和LHRH翻译。此信息 将有助于解释文献中关于 E对LHRH基因表达水平的影响为了获得这些信息，我们将 评价卵巢类固醇激素对LHRH基因改变的影响 转录(使用核连续分析和核测量 LHRH mRNA的转录本)、LHRH mRNA的细胞水平(使用原位 杂交组织化学和溶液杂交)和LHRH mRNA 翻译(通过测量LHRH前激素和十肽的比率 贯穿LHRH神经元系统。这些研究将提供 关于E和P在体内的作用机制的重要新信息 下丘脑调节黄体生成素的释放。这样的信息对 不孕不育、青春期延迟和营养不良的治疗进展 更年期症状，以及为更好和更安全的发展 避孕药。

The long-term objective of this research is to determine the neuroendocrine mechanisms by which estrogen (E) and progesterone (P) control the preovulatory surge release of luteinizing hormone (LH). Although LHRH neurons do not concentrate E or P, they act as the final common pathway by which multiple neurotransmitter systems translate information from the ovary into signals which modulate LH release. The ovarian hormone modulation of LHRH release has been studied intensively; however, little is known about the effects of E and P on LHRH biosynthesis. This information has been previously unattainable, largely because the LHRH gene had not been described, and the structure of LHRH prohormone was unknown. The present studies will use newly-developed methods and probes specific for LHRH prohormone and LHRH mRNA to determine whether LHRH biosynthesis is increased around the time of the LH surge release. The working hypothesis is that ovarian hormones stimulate de novo synthesis of LHRH before the LH surge and that LHRH hypersecretion during the surge is accompanied by elevated LHRH gene transcription. The studies proposed to test this hypothesis will also provide information regarding the relationships among LHRH transcription, steady-state LHRH mRNA levels, and LHRH translation. This information will help explain apparent discrepancies in the literature regarding the effect of E on LHRH mRNA levels. To obtain this information, we will evaluate the effects of ovarian steroids on changes in LHRH gene transcription (using nuclear run-on assays and measurements of nuclear transcripts of LHRH mRNA), cellular levels of LHRH mRNA (using in situ hybridization histochemistry and solution hybridization) and LHRH mRNA translation (by measuring ratios of LHRH prohormone and decapeptide throughout the LHRH neuronal system. These studies will provide important new information on the mechanisms by which E and P act in the hypothalamus to modulate LH release. Such information is important to the development of treatments for infertility, delayed puberty and menopausal symptoms, as well as for the development of better and safer contraceptives.