THE PHYSIOLOGICAL ROLE OF GLYCOSYLATED HUMAN PROLACTIN

惠蒂尔研究所此前的调查表明， 人脑垂体含有糖基化形式的催乳素。 这 一种新发现的催乳素形式， 天冬酰胺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 人蜕膜组织分泌糖基化催乳素体外研究 以来 初步研究表明，催乳素的糖基化改变了其 生物活性，确定影响合成的因素， 糖基化形式的分泌将提供深入了解 糖基化催乳素的生理作用。 待测试的假设 催乳素的基础分泌形式在生物学上 活性糖基化形式和活性更高的非糖基化形式 对特定刺激的反应。 使用人垂体细胞的原代培养物作为模型系统， 现在提出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，环磷酸腺苷，和 钙对正常人糖基化催乳素合成和分泌的影响 人类的垂体 还建议进行研究，以测量血清中 糖基化催乳素从正常人在各种生理 包括处于卵泡期、排卵期和黄体期的女性， 她们的月经周期、绝经后妇女、孕妇和哺乳期妇女 患有生理性高泌乳素血症的女性。 糖基化的释放 催乳素也将在促甲状腺素之后在正常志愿者中研究 释放激素、精氨酸和左旋多巴输注。 总的来说，这一建议将有助于评价新的 催乳素在正常生理中的公认形式。

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. Overall, this proposal will permit the evaluation of the role of newly recognized forms of prolactin in normal physiology.