MRNA & PEPTIDE SYNTHESIS OF VASOPRESSIN AND OXYTOCIN

信使核糖核酸

• 批准号: 3411457
• 负责人: JOSEPH T MCCABE
• 金额: $ 8.27万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411457
• 关键词: brain mapping; cell population study; hormone receptor; hypothalamus; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; messenger RNA; neuroendocrine system; neurons; neurophysiology; oxytocin; protein biosynthesis; single cell analysis; vasopressins

The proposed experiments are designed to detect, at the level of the single cell, the alterations that follow physiologically meaningful stimulation of vasopressinergic and oxytocinergic neurons. Much is known about these neurons, but previous investigations studied global alterations in levels of mRNA and proposes. Individual neurons within apparently homogeneous anatomical nuclei differ in terms of their afferent and efferent connectivity, and in terms of peptide co-localization. Hence, in approach to neuroendocrine function should be employed tbat can detact if hormone response is restricted to specific vasopressin or oxytocin cells. Utilizing quantitative in situ hybridization to determine relative amounts of vasopressin and oxytocin mRNA levels, I will examine whether all hormone-synthesizing cells within a hypothalamic cell group response to certain physiological challenges, or whether specific subgroups of cells mediate hormone response. Based upon investigations of cell connectivity, and other factors described below, it is hypothesized that hormone response is mediated by specific vasopressinergic and oxytocinergic cells. Combining in situ hybridization with immunocytochemistry for peptide co-localization, and with tract-tracing techniques, I hope to determine the dynamic, anatomical pattern of response in vivo, of these neural systems, and the basis for elucidating the salient characteristics of those cells that specifically mediate response to homeostatic challenge. In addition to providing a model for how the function of single neurons is integrated within the context of a neuroendocrine system, these studies may have clinical relevance. First, disease processes that disrupt the regulation of synthesis, transport, or release of vasopressin can precipitate inappropriate compensation of bodily fluid needs. Proposed experiments that involve water balance and how the neurohypophysial system responds are relevant. Second, vasopressin plays a role in hypertension and stress, and study of neuronal response at the single cell level will provide information regarding differential response in autonomic or neurohaemal-mediating vasopressinergic neurons compared to neurohypophysial neurons. Finally, oxytocin gene expression is an almost unexplored matter that may be clinically relevant to oxytocin's role in pregnancy, lactation, and stress.

拟议的实验旨在检测，在水平 单个细胞，生理上的改变 有意义的血管加压素和催产素刺激 神经元 我们对这些神经元了解很多，但以前 研究了mRNA水平的全球变化， 求婚 单个神经元内明显同质 解剖核团的传入和传出神经 连接性和肽共定位方面。 所以在 应采用神经内分泌功能的方法，以便能够 如果激素反应仅限于特定的血管加压素，则检测 或催产素细胞。 利用定量原位杂交 以确定加压素和催产素mRNA的相对量， 水平，我将检查是否所有的合成酶的细胞 在下丘脑细胞群中， 挑战，或者是否特定的细胞亚群介导激素 反应 基于对小区连通性的调查， 下面描述的其他因素，假设激素 反应由特异性加压素和催产素介导 细胞 原位杂交与免疫细胞化学结合 对于肽共定位，并与tract-tracing技术， 我希望能确定这种反应的动态解剖模式， 体内，这些神经系统，并阐明的基础， 这些细胞的显著特征， 对稳态挑战的反应。 除了提供一个模型如何功能单一 神经元被整合在神经内分泌的背景下， 系统，这些研究可能具有临床意义。 第一，疾病 破坏合成、运输或代谢调节的过程， 血管加压素的释放可加速不适当的代偿 体液需求。 涉及水的拟议实验 平衡和神经垂体系统如何反应是相关的。 其次，加压素在高血压和压力中起作用， 在单细胞水平上研究神经元反应将提供 关于自主或自主神经系统中的差异响应的信息 神经血液介导的加压素能神经元相比， 神经垂体神经元 最后，催产素基因的表达是一个 几乎未被探索的物质，可能与临床相关， 催产素在怀孕、哺乳和压力中的作用