REGULATION OF VASOPRESSIN AND OXYTOCIN MRNA

描述（研究者摘要）：加压素的产生 大细胞神经元的催产素有助于体内平衡， 生殖功能是至关重要的生存 个体和物种。因此，这些神经元 专门用于生产和储存大量的 激素.因此，提出了实验来检查的机制 将激素合成与激素释放结合起来以下 将讨论假设： 1-在某些条件下，VP mRNA可能是VP释放的决定因素。 这一假设将通过检查以下因素的影响来解决： 用外源义操纵VPmRNA含量和翻译， 反义VPmRNA。将在这些实验中使用分散的下丘脑培养物。 实验 2-下丘脑大细胞VP mRNA含量的调节 环磷酸腺苷（cAMP）的神经元参与调节VPmRNA 转录和周转。基因转录将在 培养分散的胎儿下丘脑神经元，通过监测 用原位杂交技术检测内含子VPmRNA的表达。的 将通过以下方法评估VP mRNA周转变化的贡献： 评价放线菌素和放线菌酮对VPmRNA含量的影响 下丘脑-神经垂体系统（HNS）的外植体。 直接用8-溴-cAMP或 间接通过用毛喉素激活腺苷酸环化酶或通过 多巴胺受体介导的腺苷酸环化酶激活 受体激动剂 3-参与OT调节的细胞内信号通路 基因表达与那些参与 调节VP基因表达。将分散的下丘脑培养物 用于确定胎儿OT表达的机制， 神经元由于许多神经系统利用肽作为化学物质， 信号，阐明合成和释放耦合的机制 神经肽在神经系统中有广泛的应用。 这些耦合过程的异常可能是神经病理学的基础。 与神经垂体系统以及其他相关的疾病 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。

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.