FUNCTION OF THE DECIDUAL TISSUE

妊娠的建立和维持需要协调 一种高度专业化的母体组织的活动：蜕膜。广泛性 我们实验室的研究揭示了一个重要的功能 大鼠蜕膜细胞的关键是它们的荷尔蒙分泌能力。我们有 显示蜕膜中特定的蜕膜细胞群起着 与垂体和卵巢相关的内分泌腺和分泌激素 激素；蜕膜催乳素相关蛋白、激活素和卵泡抑素。另一个 确定的细胞群体以丰富的α2巨球蛋白表达，a 已知的激活素结合蛋白和一种有效的蛋白酶抑制剂。这个 我们研究的总体目标是了解 蜕膜细胞信号转导系统的建立和维持 怀孕了。这笔拨款的重点是定义规则和 这些蜕膜衍生蛋白的相互作用及其在子宫内膜癌中的作用 为胎儿发育维持合适的环境。第一个具体 目的：探讨蜕膜催乳素相关蛋白的表达及其作用 蜕膜和黄体都有。我们将DPrP表示为 昆虫和细菌细胞，并研究这种激素在 孕酮代谢关键蛋白的产生和作用 和蛋白质合成。第二个目标将集中在监管和 蜕膜α2-MG基因表达的功能及判定 α2 MG与蜕膜PRL相关蛋白结合并保护其免受 退化。我们还将调查Alpha2 MG的关键角色是否 与激活素结合，防止激活素A诱导的细胞凋亡。最后，在 第三个目标，我们将检验蜕膜细胞有一个 分泌激活素A的内在能力以及激活素A刺激 表达其自身基因，并诱导细胞凋亡，导致 蜕膜的退化和重组，这是正常所必需的 胎儿发育。我们还将测试在此期间 蜕膜来源的激活素A结合α2 MG和FST的研究进展 蛋白质，阻止激活素的作用，并指导何时和在哪个细胞激活 是要表达出来的。

The establishment and maintenance of pregnancy requires the coordinated activity of a highly specialized maternal tissue: the decidua. Extensive investigation from our laboratory has revealed that one important function of rat decidual cells is their hormone-producing capabilities. We have shown that a defined decidual cell population in the decidua acts as an endocrine gland and secretes hormone related to pituitary and ovarian hormones; decidual PRL-related protein, activin and follistatin. Another defined cell population expresses in abundance alpha2 macroglobulin, a known activin-binding protein and a potent protease inhibitor. The overall objective of our research is to understand the involvement of the decidual cell signaling system in the establishment and maintenance of pregnancy. The focus of this grant is to define the regulation and interactions of these decidua-derived proteins and their role in the maintenance of the right milieu for fetal development. The first specific aim centers on the expression of decidual PRL-related protein and its role both in the decidua and in the corpus luteum. We will express dPRP in insect and bacterial cells and examine the role of this hormone on the production and action of key proteins involved in progesterone metabolism and protein synthesis. The second aim will focus on the regulation and function of the decidual alpha2 MG gene expression and determine whether alpha2 MG binds to and protects the decidual PRL-related protein from degradation. We will also investigate whether a key role of alpha2 MG is to bind to activin and prevent activin A induced apoptosis. Finally, in the third aim we will test the hypothesis that the decidual cells have an intrinsic ability to secrete activin A and that activin A stimulates the expression of its own gene and induces apoptosis, leading to the regression and reorganization of the decidua which is essential for normal fetal development. We will also test the possibility that during development alpha2 MG and FST, two decidua-derived activin A binding proteins, prevent activin action and direct when and in which cell activin is to be expressed.