PHYSIOLOGICAL ROLE OF GLYCOSYLATED HUMAN PROLACTIN

描述(改编自申请人的摘要)：催乳素(PRL)具有 据报道有许多生物作用。然而，最近的研究 这表明PRL确实是一个激素家族，每个PRL变体都有 不同的生物活动。本报告中提出的研究目的是 应用是重新评价催乳素在各种生理过程中的作用 基于存在的PRL变体的相对数量的过程。自.以来 最近的工作表明，催乳素的糖基化改变了它的生物学特性。 活性、影响合成和分泌的因素的测定 糖基化形式的研究可能有助于深入了解糖基化蛋白的生理作用 糖基化催乳素。建议的研究将集中在 人催乳素糖基化形式(G-hPRL)的分泌模式 与非糖基化形式的人催乳素(HPRL)进行比较。 其具体目的是：1)测定正常女性的G-hPRL和hPRL， 荷尔蒙催乳素血症伴溢乳和闭经的妇女，以及 高催乳素血症女性。2)使用人脑垂体原代培养物 以细胞为模型系统研究各种促分泌剂的作用 G-hPRL和hPRL的体外合成与释放3)大力发展 将针对G-hPRL或hPRL的单抗并使用 这些单抗开发了特异的免疫分析方法。4)学习 在体外培养单个垂体细胞以确定它们是否含有和 能同时分泌G-hPRL和hPRL。需要检验的假设是 特定的PRL变异体执行特定的生理功能。 这一假说意味着这种功能上的差异将被反映出来。 在G-hPRL和hPRL的不同分泌模式中。

DESCRIPTION (Adapted from the applicant's abstract): Prolactin (PRL) has been reported to have many biological actions. However, recent studies indicate that PRL really is a family of hormones, each PRL variant having different biological activities. The aim of the studies proposed in this application is to re-evaluate the role of PRL in various physiological processes based on the relative amounts of the PRL variants present. Since recent work has shown that the glycosylation of PRL alters its biological activity, determination of the factors that affect synthesis and secretion of the glycosylated form may provide insight into the physiological role of glycosylated PRL. The studies proposed will focus on the differences in the secretory patterns of the glycosylated form of human PRL (G-hPRL) in comparison to those of the nonglycosylated form of human PRL (hPRL). The specific aims are: 1) To measure G-hPRL and hPRL in normal women, hormoprolactinemic women with galactorrhea and amenorrhea, and hyperprolactinemic women. 2) To use primary cultures of human pituitary cells as a model system to investigate the effects of various secretagogues on the in vitro synthesis and release of G-hPRL and hPRL. 3) To develop monoclonal antibodies that will be specific for G-hPRL or hPRL and to use these monoclonal antibodies to develop specific immunoassays. 4) To study individual pituitary cells in vitro to determine if they contain and are capable of secreting both G-hPRL and hPRL. The hypothesis to be tested is that a specific PRL variant performs a specific physiological function. This hypothesis implies that this difference in function will be reflected in the differential secretion patterns of G-hPRL and hPRL.