THE PHYSIOLOGY OF NEUROPHYSIN SECRETION

这项赠款支持的工作集中在 神经垂体：正常功能，主要病理生理学，和 由其他疾病引起的继发性病理生理学。 我们有 开发了评估神经垂体的实验室方法 功能，并利用动物模型（大鼠）来研究 病理生理学和代谢异常的后果 功能 完全性尿崩症是众所周知的，但 部分功能丧失更为常见，但了解较少。 该补助金利用溶液杂交的新方法， 同时定量加压素和催产素mRNA， 新开发的体内翻译措施， 测量生物合成的速率，并提供时间指数， 过程前体。 体内运输的新措施类似 允许定量运输的激素以及运输 速度 每一个个体对加速的 激素运输以及运输速度。 这一切成功都 个体对加速激素释放的反应将是 在神经垂体急性损伤后进行评估， 以确定恢复的机制。 的 潜在的慢性发病率后，部分破坏的 神经垂体将通过研究 “恢复”的动物发展不适当的综合征 抗利尿剂伴低钠血症或发生尿崩症， 神经垂体受压。 在另一个模型中， 神经垂体经历急性和慢性加速 神经垂体激素的释放和随后的恢复， 响应的机制将由 消息级别、转换和传输的变化顺序。 激素合成、运输和释放的变化 还将在以下动物模型中研究神经垂体： 通过施用有效的 血管加压素类似物。 缺乏下调是一个 解释高发病率的机制 低钠血症是一种临床综合征。 免疫组织 技术和原位杂交将被用来直接 识别参与损伤恢复的神经元， 是否有新的神经元被募集和/或是否有新的 神经支配在原始神经元上发展， 原始神经元会根据需要改变其大小和形状 增加分泌物。 在损伤大鼠中的研究直接 人类机能障碍的原因 正在进行的临床研究 这些项目与我们对 神经垂体的病理生理学，毫无疑问 对压力的反应与本研究中研究的机制相同。 赠款将继续。 该基金会带来了分子生物学的新工具， 生物学的直接临床问题的调查 相关性，并将增加我们对 神经垂体损伤，加速激素释放， 以及抑制激素释放。

Work supported by this grant has concentrated on the neurohypophysis: normal function, primary pathophysiology, and secondary pathophysiology produced by other disorders. We have developed laboratory methods of assessing neurohypophyseal function and have utilized animal models (rats) to study the pathophysiology and metabolic consequences of abnormal function. Complete diabetes insipidus is well understood, but partial loss of function is more common and less well understood. This grant utilizes new methods of solution hybridization to simultaneously quantitate mRNA of vasopressin and oxytocin, and newly developed in vivo measures of translation which will measure rate of biosynthesis and provide an index of time to process precursors. New measures of in vivo transport similarly allow quantitation of hormone transported as well as transport velocity. Each of these individual responses to accelerated hormone transported as well as transport velocity. Each of these individual responses to accelerated hormone release will be evaluated after damage to the neurohypophysis acutely and chronically to determine the mechanism of recovery. The potential for chronic morbidity after partial destruction of the neurohypophysis will be investigated by studying the risk of "recovered" animals to develop the syndrome of inappropriate antidiuresis with hyponatremia or develop diabetes insipidus when the neurohypophysis is stressed. In another model where the neurohypophysis undergoes acute and then chronic accelerated release of neurohypophyseal hormones and subsequent recovery, the mechanism of the response will be determined by the sequence of changes in message levels, translation, and transport. Changes in hormone synthesis, transport and release in the neurohypophysis will also be investigated in an animal model of chronic suppression of AVP by administration of a potent vasopressin analogue, DDAVP. Lack of down-regulation is a proposed mechanism to explain the high incidence of hyponatremia as a clinical syndrome. Immunohistologic techniques and in situ hybridization will be employed to directly identify the neurons which are involved in recovery from damage, whether new neurons are recruited and/or whether new innervation develops on the original neurons and whether the original neurons change their size and shape in response to need for increased secretion. The studies in lesioned rats are directly attributable to human dysfunction. Ongoing clinical research projects which are relevant to our understanding of the pathophysiology of the neurohypophysis and which undoubtedly respond to stress by the same mechanisms investigated in this grant will be continued. The grant brings new tools of molecular biology to the investigation of problems of immediate clinical relevance and will increase our understanding of the response of the neurohypophysis to injury, to accelerated hormone release, and to inhibition of hormone release.