THE PHYSIOLOGICAL ROLE OF GLYCOSYLATED HUMAN PROLACTIN

惠蒂尔研究所此前的调查表明， 人类脑下垂体含有一种糖基化形式的催乳素。这 新发现的催乳素含有一个碳水化合物单位 天门冬酰胺31。我们还发现，糖基化催乳素存在于 人血清和羊水，以及人垂体细胞和 人蜕膜组织体外分泌糖基化催乳素。自.以来 初步研究表明，催乳素的糖基化改变了它的 生物活性，影响合成的因素的测定和 糖基化形式的分泌将提供对 糖基化催乳素的生理作用。需要检验的假设 催乳素的基本分泌形式在生物学上 活性糖基化形式和更活跃的非糖基化形式 对特定刺激的反应而释放的。 以人垂体细胞原代培养为模型系统， 现在有人提议用实验来研究促甲状腺激素的作用。 释放激素、溴隐亭、多巴胺、雌激素、环状AMP和 钙对正常人糖基化催乳素合成和分泌的影响 人类脑下垂体。还建议进行研究以测量血清中的 正常人不同生理状态下的糖基化催乳素 包括处于卵泡期、排卵期和黄体期的妇女 她们的月经周期、绝经后妇女、怀孕和护理 患有生理性高催乳素血症的女性。糖基化药物的释放 促甲状腺激素后，催乳素也将在正常志愿者中进行研究 释放激素、精氨酸、L-多巴输液。此外，血清 糖基化催乳素将在高催乳素血症患者中进行检测 没有腺瘤。 总体而言，这项提案将允许评价新的 催乳素在正常生理和某些特定情况下的识别形式 病理状态，如各种形式的高催乳素血症。

Previous investigations from The Whittier Institute have demonstrated that human pituitary glands contain a glycosylated form of prolactin. This newly recognized form of prolactin contains a carbohydrate unit on asparagine 31. We have also shown that glycosylated prolactin is found in human serum and amniotic fluid and that both human pituitary cells and human decidual tissue secrete glycosylated prolactin in vitro. Since preliminary studies have shown that glycosylation of prolactin alters its biological activity, determination of the factors that affect synthesis and secretion of the glycosylated form will provide insight into the physiological role of glycosylated prolactin. The hypothesis to be tested is that the basal secretory form of prolactin is the less biologically active glycosylated form and that the more active, nonglycosylated form is released in response to specific stimuli. Using primary cultures of human pituitary cells as a model system, experiments are now proposed to investigate the effects of thyrotropin releasing hormone, bromocriptine, dopamine, estrogen, cylic AMP, and calcium on the synthesis and secretion of glycosylated prolactin by normal human pituitaries. Studies are also proposed to measure serum levels of glycosylated prolactin from normal individuals in various physiological states including women in the follicular, ovulatory, and luteal phases of their menstrual cycles, post-menopausal women, and pregnant and nursing women with physiologic hyperprolactinemia. The release of glycosylated prolactin will also be studied in normal volunteers after thyrotropin releasing hormone, arginine and L-dopa infusion. In addition, serum glycosylated prolactin will be measured in hyperprolactinemics with and without adenomas. Overall, this proposal will permit the evaluation of the role of newly recognized forms of prolactin in normal physiology and in certain pathologic conditions such as the various forms of hyperprolactinemia.