THE PHYSIOLOGY OF NEUROPHYSIN SECRETION

这项资助的目的一直是为了了解神经物理药物( 生理学中的加压素和催产素的神经元内载体蛋白 和疾病。我们从人的脑下垂体中分离出两种神经生理素， 对每种药物进行了特异性放射免疫分析，并证明了每种神经物理素 独立分泌的。建立了加压素和催产素的分析方法 记录荷尔蒙和神经物理素的平行分泌。氨基酸 神经内科药物序列证明，加压素-神经内科药物和 所有物种的催产素-神经内分泌蛋白都有共同的序列。当前 人们认为，神经内科药物是共同前体的一部分，从这些前体中 形成了一种荷尔蒙特有的神经物理素和一种荷尔蒙。通过化验 它是我们用蛋白质化学的标准技术开发的 我们可以在人和大鼠的脑下垂体中鉴定出神经物理素的前体。我们 现在将从人类脑下垂体中分离出足够的神经物理素前体 对蛋白质进行表征，研究其转化为神经物理蛋白和 荷尔蒙，并建立前体的放射免疫分析。在 人类先兆可作为癌症标记物和病理证据 荷尔蒙分泌。在大鼠体内，前体可以用来识别比率 荷尔蒙的合成、运输和释放。前驱体的含量 大鼠的下丘脑和垂体将在已知状态下进行测量 催产素和加压素的高分泌以确定哪些因素 控制神经垂体功能。我们亦会研究 “耗尽/再耗尽”现象，即大鼠试图维持 激素在垂体后叶的恒定储存，尽管 或荷尔蒙释放减少。我们将衡量以下内容 脑下垂体中的神经生理素、加压素和催产素 耗尽和再耗尽。我们将把合成的产品注入 (加压素、催产素和神经物理素)和神经递质进入大脑 下丘脑是荷尔蒙合成的地方，并测量 输液对耗竭/再耗竭现象有更好的认识 开启和关闭神经垂体激素生物合成的因素。这个 信息将有助于理解缺乏分泌物或 人类疾病中的加压素(和催产素)过度分泌。

The aim of this grant has been to understand the role of neurophysins (the intraneuronal carrier proteins of vasopressin and oxytocin) in physiology and disease. We isolated two neurophysins from human pituitary, developed specific radioimmunoassays for each, and demonstrated each neurophysin was independently secreted. Assays for vasopressin and oxytocin were developed to document parallel secretion of hormone and neurophysin. Amino acid sequence of neurophysins proved that the vasopressin-neurophysins and the oxytocin-neurophysins in all species shared common sequence. Current thinking is that neurophysins are part of a common precursor from which are formed a hormone specific neurophysin and one hormone. With the assays which we have developed and with standard techniques of protein chemistry we can identify precursors of neurophysin in human and rat pituitary. We will now isolate sufficient precursor neurophysin from human pituitary to characterize the protein, to study its conversion to neurophysin and hormone, and to develop a radioimmunoassay for the precursor. In the human, precursors may serve as cancer markers and as evidence of pathologic secretion of hormone. In the rat, precursors can be used to identify rates of synthesis, transport and release of hormone. Content of precursor in the rat hypothalamus and pituitary will be measured in states of known hypersecretion of oxytocin and vasopressin to identify factors which control neurohypophyseal function. We will also study the "depletion/repletion" phenomenon whereby the rat attempts to maintain a constant store of hormone in the posterior pituitary in spite of increased or decreased release of hormone. We will measure the content of neurophysin, vasopressin and oxytocin in the pituitary to document depletion and repletion. We will infuse the products of synthesis (vasopressin, oxytocin and neurophysin) and neurotransmitters into the hypothalamus where the hormones are synthesized and measure the effect of the infusion on the depletion/repletion phenomenon to better understand the factors which turn on and off neurohypophyseal hormone biosynthesis. The information will help to understand the lack of secretion or the oversecretion of vasopressin (and oxytocin) in human disease.