EFFECT OF PLACENTAL LACTOGEN ON UTERINE FUNCTION

胎盘泌乳素对子宫功能的影响

• 批准号: 2202211
• 负责人: LINDA A. SCHULER
• 金额: $ 10.06万
• 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 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2202211
• 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; mitogen activated protein kinase; northern blottings; nuclear runoff assay; nucleic acid hybridization; nucleic acid sequence; phosphorylation; polymerase chain reaction; pregnancy; 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.

子宫胎盘单位产生许多激素，据信这些激素 协调成功怀孕。 在人类和反刍动物中， 这些包括生长激素的进化亲属和 催乳素，胎盘催乳素（PL）。 与垂体类比 激素，相关的胎盘激素可能在多种方面发挥作用 胎儿发育过程结束母体适应 怀孕。 我们的长期目标是了解这些的功能 妊娠期相关胎盘激素及其作用方式，以及 组织末端激素特异性的基础。 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， 是明显的局部配体。为了研究胎盘的作用 子宫上的催乳素，并研究激素信号的介导，我们 开发了同源子宫细胞原代培养的方法。 激素特异性受体的表达和反应能力 荷尔蒙刺激是该模型的特征，它提供了 剖析母胎复杂性的独特机会 互动。在这些研究中，我们将把注意力集中在 bPL 对溶基质素转录物水平的调节。我们将 描述上皮细胞中基质溶解素对 bPL 的反应 关于bPL作用于表达的时间、浓度、位点 这个基因，以及介导这种反应的受体。我们将评估 其他细胞因子和生长因子在调节中的作用 子宫细胞中基质溶解素的表达及其与 PL。为了研究 bPL 对转录的刺激，我们将 通过突变鉴定溶基质素启动子中的顺式作用序列 分析和凝胶位移论文。最后我们来检验一下效果 通过检查酪氨酸对已知信号转导途径进行 bPL 磷酸化和 MAP 激酶活性。 这些研究将有助于我们了解 PL 和 怀孕期间子宫相关激素，增长我们的知识 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。