EFFECT OF PLACENTAL LACTOGEN ON UTERINE FUNCTION

胎盘泌乳素对子宫功能的影响

• 批准号: 3331343
• 负责人: LINDA A. SCHULER
• 金额: $ 9.46万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3331343
• 关键词: SDS polyacrylamide gel electrophoresis; biological signal transduction; cytokine; gel mobility shift assay; genetic regulatory element; genetic transcription; growth factor; high performance liquid chromatography; hormone receptor; hormone regulation /control mechanism; microtubule associated protein; northern blottings; nuclear runoff assay; nucleic acid hybridization; nucleic acid sequence; phosphorylation; polymerase chain reaction; pregnancy; protein tyrosine kinase; receptor expression; somatomammotropin; southern blotting; stromelysin; tissue /cell culture; uterus

The utero-placental unit produces many hormones which are believed to coordinate the successful pregnancy. In humans as well as ruminants, these include the evolutionary relatives of growth hormone and prolactin, placental lactogens (PL). By analogy to the pituitary hormones, the related placental hormones may play a role in a variety of processes in fetal development end maternal adaptations to pregnancy. Our long term goal is to understand the function of these related placental hormones in pregnancy, their mode of action, and basis for tissue end hormone specificity. Recently, three receptors for this hormone family have been described in the uterus. These placental hormones, including placental lactogen, are obvious local ligands. In order to study the actions of placental lactogen on the uterus, and study mediation of the hormonal signal, we have developed methods for primary culture of homologous uterine cells. The expression of hormone-specific receptors and the ability to respond to hormonal stimuli are characteristics of this model which offer an unique opportunity to dissect the complexities of maternal-fetal interactions. In these studies, we will focus our attention on modulation by bPL of the level of transcripts for stromelysin. We will describe the stromelysin response to bPL in epithelial cells with respect to time, concentration, site of bPL action on expression of this gene, and the receptors mediating this response. We will evaluate the role of other cytokines and growth factors in regulation of stromelysin expression in uterine cells, and their interactions with PL. In order to investigate bPL stimulation of transcription, we will identify cis-acting sequences in the stromelysin promoter by mutational analysis and gel shift essays. Finally, we will examine the effect of bPL on known signal transduction pathways by examining tyrosine phosphorylation and MAP kinase activities. These studies will aid in our understanding of the function of PL and related hormones in the uterus during pregnancy, increase our knowledge of signal transduction of this little-understood family of receptors, and integrate the GH/PRL gene family and their receptors into the cytokine network.

子宫-胎盘单位会产生许多荷尔蒙，据信 配合成功妊娠。在人类和反刍动物中， 这些包括生长激素和生长激素的进化近亲 催乳素、胎盘催乳素(PL)。比喻为脑下垂体 激素，相关的胎盘激素可能在多种疾病中发挥作用 胎儿发育过程结束母体适应 怀孕了。我们的长期目标是了解这些系统的功能 妊娠中相关的胎盘激素及其作用方式，以及 组织终末激素特异性的基础。 最近，该激素家族的三种受体已被描述。 在子宫里。这些胎盘激素，包括胎盘催乳素， 都是明显的局部配体。为了研究胎盘的作用 催乳素对子宫的作用，并研究荷尔蒙信号的调节，我们 已经开发出同种子宫细胞的原代培养方法。 激素特异性受体的表达与免疫应答能力 荷尔蒙刺激是这种模式的特点，它提供了一种 独一无二的机会剖析母婴的复杂性 互动。在这些研究中，我们将把注意力集中在 BPL对基质分解素转录本水平的调节。我们会 描述上皮细胞中基质分解素对BPL的反应 BPL作用的时间、浓度、部位对其表达的影响 该基因和介导这一反应的受体。我们将评估 其他细胞因子和生长因子在调节血管内皮细胞生长中的作用 基质分解素在子宫细胞中的表达及其与细胞因子的相互作用 Pl.为了研究BPL对转录的刺激，我们将 突变鉴定基质分解蛋白启动子中的顺式作用序列 分析和凝胶变换论文。最后，我们将检查以下内容的效果 酪氨酸对已知信号转导通路中BPL的影响 磷酸化和MAP激酶活性。 这些研究将有助于我们对物流的功能和功能的理解 怀孕期间子宫中的相关激素，增加我们的知识 关于这个鲜为人知的受体家族的信号转导， 并将GH/PRL基因家族及其受体整合到 细胞因子网络。