BRAIN PROLACTIN AS A CENTRAL NEUROMODULATOR

作为本实验室其他工作的逻辑延伸， 在大鼠中枢神经系统中发现垂体前叶神经元样蛋白 神经系统，免疫反应性和生物活性的存在 据报道，催乳素广泛分布于大鼠脑内。 这种基于脑的催乳素样免疫反应性（PLI）， 免疫学、色谱学和生物学上与 垂体前叶催乳素，不依赖于前叶 垂体的存在，并在下丘脑，主要是 与突触体有关。 在本项目期间，我们建议 将这项工作扩展到测试两个假设，即： 1. 脑催乳素是一种局部合成的， 神经调质/神经递质。 2. 下丘脑催乳素，与睾丸激素共同作用， 刺激下丘脑β-内啡肽分泌。 这种效果是 部分通过刺激多巴胺释放来介导。 支持第一个假设的数据来自于 实验设计：1）直接和间接评估 是否有催乳素的原位脑合成; 2） 确定下丘脑外脑中的催乳素是否 集中在神经末梢（如下丘脑催乳素）;以及 3)为了在体外建立催乳素可以从 下丘脑和下丘脑外脑部分的钾- 以钙依赖性方式诱导去极化。 到 证明大脑催乳素具有这些属性， 强烈支持第一个假设。 而且还要 确定获得催乳素的个体发育模式， 下丘脑和下丘脑外的离散区域 脑，并将此配置文件与垂体中的催乳素和 血清的 这项实验将涉及从胎儿到老年的动物 年龄 这些数据将提供重要的描述性信息， 信息，也影响了第一个假设，因为 神经递质通常在个体发育早期出现，因此， 在胎儿生命早期出现脑催乳素将支持 神经递质状态 此外，演示离散 内源性下丘脑催乳素的神经化学作用， 尽管在操作上被列为单独的第二假设， 会支持第一个假设

As a logical extension of other work from this laboratory on anterior pituitary hormone-like proteins found in rat central nervous system, the presence of an immunoreactive and bioactive prolactin widely distributed in the rat brain has been reported. This brain-based prolactin-like immunoreactivity (PLI), which is immunologically, chromatographically, and biologically similar to anterior pituitary prolactin, is not dependent on the anterior pituitary for its presence, and in hypothalamus, is largely associated with synaptosomes. In this project period we propose to extend this work to test two hypotheses, namely: 1. Brain prolactin is a locally synthesized, central neuromodulator/neurotransmitter. 2. Hypothalamic prolactin, acting together with testosterone, stimulates hypothalamic beta-endorphin secretion. This effect is partly mediated through stimulation of dopamine release. Data to support the first hypothesis will be derived from experiments designed: 1) to both directly and indirectly assess whether there is in situ brain synthesis of prolactin; 2) to determine whether prolactin in the extrahypothalamic brain is concentrated at nerve endings (as is hypothalamic prolactin); and 3) to establish in vitro that prolactin can be released from hypothalamic and extrahypothalamic brain parts by potassium- induced depolarization in a calcium dependent fashion. To demonstrate that brain prolactin possesses these attributes would strongly support the first hypothesis. Moreover, we will determine the ontogenetic pattern of acquisition of prolactin in the hypothalamus and in discrete areas of extrahypothalamic brain and compare this profile to that of prolactin in pituitary and serum. This experiment will involve animals from fetal life to old age. This data, which will provide important descriptive information, also impacts on the first hypothesis since neurotransmitters generally appear early in ontogenesis and, thus, appearance of brain prolactin early in fetal life would support a neurotransmitter status. In addition, demonstration of discrete neurochemical effects of endogenous hypothalamic prolactin, although listed operationally as a separate second hypothesis, would support the first hypothesis.