PHYSIOLOGICAL ROLE OF GLYCOSYLATED HUMAN PROLACTIN

描述（改编自申请人摘要）：催乳素（PRL）具有 据报道，它具有许多生物学作用。 但最近的研究 表明PRL确实是一个激素家族，每个PRL变体具有 不同的生物活动。 本文提出的研究目的是 应用是重新评估PRL在各种生理中的作用， 基于存在的PRL变体的相对量进行处理。 以来 最近的研究表明，PRL的糖基化改变了其生物学特性， 活性，影响合成和分泌的因素的测定 的糖基化形式可以提供洞察的生理作用， 糖基化PRL 拟议的研究将侧重于 人PRL糖基化形式（G-hPRL）的分泌模式， 与非糖基化形式的人PRL（hPRL）的那些相比。 具体目的是：1）测定正常妇女的G-hPRL和hPRL， 泌乳过多和闭经的激素促乳素血症女性，以及 高催乳素血症的女性 2)用原代培养的人垂体 细胞作为模型系统，以研究各种促分泌素的作用 对G-hPRL和hPRL体外合成和释放的影响。 3)发展 对G-hPRL或hPRL具有特异性的单克隆抗体， 这些单克隆抗体开发特定的免疫测定。 4)研究 单个垂体细胞在体外，以确定它们是否含有和 能够分泌G-hPRL和hPRL。 待检验的假设是 特定的PRL变体执行特定的生理功能。 这一假设意味着这种功能上的差异将反映在 G-hPRL和hPRL的不同分泌模式。

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.