BIOLOGY OF THE PLACENTAL PROLACTIN FAMILY

胎盘催乳素家族的生物学

• 批准号: 3330575
• 负责人: MICHAEL J SOARES
• 金额: $ 14.06万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3330575
• 关键词: CHO cells; amnion; bioassay; biological transport; genetic manipulation; growth /development; hormone binding protein; hormone receptor; hormone regulation /control mechanism; immunochemistry; laboratory rabbit; laboratory rat; mammalian embryology; peptide hormone analog; placental hormones; pregnancy; prolactin; protein purification; radioimmunoassay; receptor binding; recombinant DNA; somatomammotropin; somatotropin; tissue /cell culture; transfection; trophoblast

Normal progression of growth and maturation of the fetus requires concomitant maternal metabolic adjustments. Trophoblast cells and their secretory products provide the signalling system that coordinates the activities of fetal and maternal tissues. At present, our understanding of the trophoblast signalling system is poor. The goal of this research is to further our understanding of an important family of regulatory proteins produced by trophoblast cells. These placental proteins are all structurally related to pituitary prolactin (PRL). We hypothesize that this family of placental proteins is involved in directing the physiological adaptations of maternal and fetal tissues that occur during pregnancy in the rat. In the rat, a total of six distinct members of the placental PRL family have been identified and partially characterized. The biological actions of four members, PRL-like protein-A (PLP-A), PLP-B, PLP-C, and placental lactogen-I variant (PL-Iv) are unknown. These four proteins are synthesized in abundant amounts and represent the major placental secretory proteins of the second half of pregnancy. Specifically, we propose to: 1) generate and characterize recombinant PLP- A, PLP-B, PLP-C, and PL-Iv proteins; 2) examine the distribution of PLP-A, PLP-B, PLP-C, and PL-Iv in maternal, fetal, and amniotic compartments; 3) evaluate the PRL- and GH-like biological activities of PLP-A, PLP-B, PLP-C, and PL-Iv. Molecular biology, protein chemistry, immunochemistry and cell culture techniques will be used to elucidate the biological activities of these four members of the placental PRL gene family. It is important to appreciate that disruptions in the coordination of fetal and maternal activities are potential causes of abnormal development. Thus, the inappropriate expression or action of members of the placental PRL family may have significant consequences on embryonic/fetal development.

胎儿的生长和成熟的正常进展需要 伴随孕产妇代谢调整。 滋养细胞及其 分泌产品提供了协调的信号系统 胎儿和母体组织的活性。 目前，我们对 滋养细胞信号系统很差。 这项研究的目的是进一步我们对重要的理解 由滋养细胞产生的调节蛋白家族。 这些 胎盘蛋白在结构上与垂体催乳素有关 （prl）。 我们假设该胎盘蛋白涉及该家族 指导母体和胎儿组织的生理适应 这在大鼠怀孕期间发生。 在老鼠中，总共六个 已经确定了胎盘prl家族的不同成员 部分表征。 四个成员，类似于PRL的生物学行为 蛋白质A（PLP-A），PLP-B，PLP-C和胎盘乳元I变体（PL-IV） 是未知的。 这四种蛋白质大量合成，并且 代表下半年的主要胎盘分泌蛋白 怀孕。 具体而言，我们建议：1）生成和表征重组PLP- A，PLP-B，PLP-C和PL-IV蛋白； 2）检查PLP-A的分布， 在母体，胎儿和羊水区中，PLP-B，PLP-C和PL-IV； 3） 评估PLP-A，PLP-B，PLP-C的PRL和GH样生物学活性 和PL-IV。 分子生物学，蛋白质化学，免疫化学和细胞 文化技术将用于阐明 这四个胎盘PRL基因家族的成员。 重要的是要欣赏胎儿协调的破坏 孕产妇活动是异常发展的潜在原因。 因此，胎盘成员的不当表达或行动 PRL家族可能会对胚胎/胎儿产生重大影响 发展。