HORMONE CONTROL OF PREPROTACHYKININ-A GENE EXPRESSION

细胞与细胞之间的通讯通常是由肽介导的， 神经和外周组织。 肽合成的调节是 控制这种交流的重要一步。 这 应用程序检查调节两个相关的合成过程 肽，物质P（SP）和物质K（SK），使用分子 生物技术 SP和SK由相同的 前前速激肽-A（PPT-A）基因，并选择性分布 神经和内分泌组织包括垂体前叶 实验将检查SP的激素和神经调节 和SK浓度和PPT-A基因的表达， 垂体前叶和几个离散的神经部位。 这些 实验分为四个领域： 1)SP和SK含量以及PPT-A mRNA丰度受到调节 由甲状腺激素和性类固醇激素在前部 脑垂体 拟议的实验将确定PPT-A mRNA 丰度与PPT-A基因或PPT-A的转录有关 mRNA降解。 2)尾状核SP浓度和PPT-A mRNA丰度 壳核受多巴胺和阿片类药物调节。 在其他神经 区域，包括下丘脑、杏仁核和视前区， SP浓度在发情周期和发情后的变化 性腺切除术 实验将确定激素是否调节 PPT-A基因在神经组织中的表达。 3)初级PPT-A RNA转录物经历一系列的 交替剪接以产生三个成熟的PPT-A mRNA。 组织 和亚细胞定位的PPT-A mRNA进行检查， 确定是否存在组织和/或组织诱导的差异 在他们的分布。 4)实验将确定顺式作用元件是否与 与PPT-A基因赋予激素调节其表达。 这些研究将阐明表达的机制， PPT-A基因在内分泌和神经组织中受到调节， 提高对肽生产的理解， 在分子水平上受激素调节。

Cell-to-cell communication is often subserved by peptides in neural and peripheral tissues. Regulation of peptide synthesis is an important step controlling this communication. This application examines processes regulating synthesis of two related peptides, substance P (SP) and substance K (SK), using molecular biological techniques. SP and SK are encoded by the same preprotachykinin-A (PPT-A) gene and are selectively distributed in neural and endocrine tissues, including the anterior pituitary. Experiments will examine hormonal and neural regulation of SP and SK concentrations and expression of the PPT-A gene in anterior pituitary and several discrete neural sites. These experiments are divided into four areas: 1) SP and SK content and PPT-A mRNA abundance are regulated by thyroid hormone and sex steroid hormones in the anterior pituitary. Proposed experiments will determine if PPT-A mRNA abundance is related to transcription of the PPT-A gene or PPT-A mRNA degradation. 2) SP concentration and PPT-A mRNA abundance in caudate putamen is regulated by dopamine and by opiates. In other neural regions, including hypothalamus, amygdala and preoptic regions, SP concentrations change during the estrous cycle and after gonadectomy. Experiments will determine if hormones regulate PPT-A gene expression in neural tissues. 3) The primary PPT-A RNA transcript undergoes a series of alternate splicings to yield three mature PPT-A mRNAs. Tissue and subcellular localization of PPT-A mRNAs be examined to determine if there are tissue and/or hormone-induced differences in their distribution. 4) Experiments will determine if cis-acting elements associated with the PPT-A gene confer hormonal regulation to its expression. These studies will elucidate mechanisms by which expression of the PPT-A gene is regulated in endocrine and neural tissues and enhance understanding of how production of peptides can be regulated by hormones at the molecular level.