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 控制排卵前促黄体激素（LH）的激增释放。 虽然LHRH神经元不集中E或P，但它们充当最终的神经元。 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LH释放的信号。 的 卵巢激素对LHRH释放的调节作用已被深入研究; 然而，关于E和P对LHRH的影响， 生物合成 这些信息以前是无法获得的， 因为LHRH基因还没有被描述，LHRH的结构 激素原未知。 本研究将使用新开发的 特异于LHRH激素原和LHRH mRNA的方法和探针， 确定LHRH生物合成是否在LHRH的时间前后增加， LH激增释放。 目前的假设是卵巢激素 在LH峰之前刺激LHRH从头合成， 激增期间的高分泌伴随着LHRH基因升高 转录。 为检验这一假设而提出的研究也将 提供关于LHRH转录之间关系的信息， 稳态LHRH mRNA水平和LHRH翻译。 这些信息 这将有助于解释在文献中关于 E对LHRH mRNA水平的影响。 为了获得这些信息，我们将 评价卵巢激素对LHRH基因变化的影响 转录（使用核连续测定和核转录的测量） LHRH mRNA的转录物），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激素原和十肽 在LHRH神经系统中。 这些研究将提供 重要的新信息的机制，其中E和P的行为， 下丘脑调节LH释放。 这些信息对于 不孕症、青春期延迟和 更年期症状，以及发展更好，更安全 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.