REGULATION OF VASOPRESSIN AND OXYTOCIN MRNA

加压素和催产素 mRNA 的调节

• 批准号: 2037371
• 负责人: CELIA D SLADEK
• 金额: $ 22.29万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2037371
• 关键词: adenylate cyclase; cyclic AMP; embryo /fetus tissue /cell culture; gene expression; genetic transcription; hormone regulation /control mechanism; hypothalamic pituitary axis; hypothalamus; in situ hybridization; introns; laboratory rat; messenger RNA; neurohypophysis; oxytocin; peptide hormone biosynthesis; secretion; vasopressins

DESCRIPTION (Investigator's Abstract): The production of vasopressin and oxytocin by magnocellular neurons subserves homeostatic and reproductive functions which are critical to the survival of the individual as well as the species. As a result, these neurons are specialized for the production and storage of large quantities of hormone. Therefore, experiments are proposed to examine the mechanisms that couple hormone synthesis to hormone release. The following hypothesis will be addressed: 1- Under certain conditions, VP mRNA can be a determinant of VP release. This hypothesis will be addressed by examining the effect of manipulating VPmRNA content and translation with exogenous sense and antisense VPmRNA. Dispersed hypothalamic cultures will be used in these experiments. 2- The regulation of VP mRNA content in hypothalamic magnocellular neurons by cyclic AMP(cAMP) involves regulation of both VPmRNA transcription and turnover. Gene transcription will be evaluated in cultures of dispersed fetal hypothalamic neurons by monitoring the expression of intronic VPmRNA using in situ hybridization. The contribution of alterations in VP mRNA turnover will be assessed by evaluating the effect of actinomycin and cycloheximide on VPmRNA content of explants of the hypothalamo-neurohypophyseal system (HNS). Intracellular cAMP will be elevated either directly with 8-bromo-cAMP or indirectly through activation of adenyl cyclase with forskolin or by receptor mediated activation of adenyl cyclase with a D1 dopamine receptor agonist. 3- The intracellular signaling pathways involved in the regulation of OT gene expression are fundamentally different from those involved in regulating VP gene expression. Dispersed hypothalamic cultures will be used to identify the mechanisms responsible for OT expression by fetal neurons. Since numerous neuronal systems utilize peptides as chemical signals, elucidation of the mechanisms coupling synthesis and release of neuropeptides has broad application to the nervous system. Abnormalities in these coupling processes may underlie neuropathological conditions associated with the neurohypophyseal system as well as other neuronal systems. Therefore, the proposed studies will provide important insight into normal and pathological processes in the nervous system.

描述(研究人员摘要)：加压素的产生 而大细胞神经元的催产素抑制了动态平衡和 对生物生存至关重要的生殖功能 无论是个体还是物种。因此，这些神经元是 专门用于生产和储存大量的 荷尔蒙。因此，提出了用实验来检验这种机制。 将荷尔蒙合成和荷尔蒙释放结合起来。以下是 我们将讨论以下假设： 1-在一定条件下，VP信使核糖核酸可作为VP释放的决定因素。 这一假设将通过检验以下因素的影响来解决 用外源感觉和翻译操纵VPmRNA的含量和翻译 反义VPmRNA。分散的下丘脑培养物将用于这些 实验。 下丘脑大细胞内VP mRNA含量的调节 环磷酸腺苷(CAMP)诱导的神经元参与VPmRNA的调节 转录和营业额。基因转录将在#年进行评估 体外培养分散的胎儿下丘脑神经元 用原位杂交法表达内含子VPmRNA。这个 VP mRNA周转率变化的贡献将通过以下方式进行评估 放线菌素和放线菌亚胺对VPmRNA含量的影响 下丘脑-神经垂体系统(HNS)的外植体。 用8-溴-cAMP或8-溴-cAMP直接升高细胞内cAMP 间接地通过用Forsklin激活腺苷环化酶或通过 受体介导的腺苷环化酶与多巴胺的相互作用 受体激动剂。 3-参与OT调控的细胞内信号通路 基因表达从根本上不同于那些涉及 调节VP基因的表达。分散的下丘脑培养物将是 用于确定导致胎儿OT表达的机制 神经元。由于许多神经系统利用多肽作为化学物质 信号，解释合成和释放的耦合机制 神经肽在神经系统中有着广泛的应用。 这些耦合过程中的异常可能是神经病理的基础。 与神经垂体系统相关的疾病以及其他 神经系统。因此，拟议的研究将提供重要的 深入了解神经系统的正常和病理过程。