BRAIN PROLACTIN AS A CENTRAL NEUROMODULATOR

作为本实验室中其他工作的合理延伸 大鼠中枢神经系统中的垂体前叶激素样蛋白 神经系统，免疫活性和生物活性的存在 催乳素广泛分布于大鼠脑内已有报道。 这种基于大脑的催乳素样免疫反应(PLI)，是 在免疫学、层析和生物学上类似于 垂体前叶催乳素，不依赖于前叶 垂体腺的存在，以及下丘脑，很大程度上是 与突触体相关。在这个项目期间，我们建议 为了扩展这项工作以检验两个假设，即： 1.脑内催乳素是局部合成的、中枢的 神经调节剂/神经递质。 2.下丘脑催乳素与睾酮共同作用， 刺激下丘脑β-内啡肽的分泌。这种效果是 部分通过刺激多巴胺释放而起作用。 支持第一个假设的数据将来自 设计的实验：1)直接和间接评估 脑内是否有催乳素的原位合成；2) 确定下丘脑外脑中的催乳素是否 集中在神经末梢(下丘脑催乳素也是如此)； 3)在体外建立催乳素可以从 下丘脑和下丘脑外脑部分由钾组成 以钙依赖的方式诱导去极化。至 证明大脑中的催乳素具有这些属性 强烈支持第一种假设。此外，我们还将 确定大鼠催乳素获取的个体发育模式 下丘脑和下丘脑外的离散区域 并将其与垂体腺和脑组织中催乳素的分布进行比较。 血清。这项实验将涉及从胎儿期到老年的动物 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 神经递质通常出现在个体发育的早期，因此， 胎儿期早期脑部催乳素的出现将支持 神经递质状态。此外，还演示了离散化 内源性下丘脑催乳素的神经化学效应 尽管在操作上被列为单独的第二个假设， 会支持第一种假设。

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.