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MODULATION OF THE PI-PATHWAY IN PREGNANT MYOMETRIUM

妊娠子宫肌层中 PI 通路的调节

基本信息

批准号：
2889140
负责人：
Mark Phillippe
金额：
$ 19.86万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-05-07 至 2001-04-30
项目状态：
已结题

项目摘要

The phosphatidylinositol (PI) -signaling pathway plays an essential role during the intracellular signal transduction events occurring in nonexcitable cells in response to various hormones and neurotransmitters. Previous studies from my lahoratory have demonstrated that the PI- signaling pathway also plays a significant role during the generation of the cytosolic calcium oscillation-like phenomena that underlie phasic myometrial contractions. Phosphoinositidespecific phospholipase C (PI- PLC), protein kinase C (PKC), and diacylglycerol lipase (DAG-L), key enzymes involved in the PI-signaling pathway, are expressed in pregnant rat myometrium; expression that appears to be modulated during the latter third of gestation. Although temporaIly refated to the fall in progesterone and rise in estradiol occurring during the same period of gestation in the pregnant rat, the specific events responsible for the gestational modulation of these signal transduction enzymes are undefined. This study proposes to test the hypothesis that estradiol and/or progesterone specifically regulate the activity and expression of these key signal transduction enzymes in pregnant rat myometrium. The SPECIFIC MMS for this revised application are: 1) evaluate the effects of gestation and steroid hormones on the activity and expression of PI-PLC, 2) evaluate the effects of gestation and steroid hormones on the activity and expression of PKC, and 3) evaluate the effects of gestation and steroid hormones on the activity of the enzymes that metabolically inactivate DAG (ie. DAG-L and diacylglycerol kinase (DAG-K)). These studies will be performed utilizing rat myometrial tissue obtained during normal gestation, from pregnant rats undergoing steroid hormone manipulation in vivo, from pseudopregnant rats, and tissue cultures stimulated in vitro with steroid hormones. These proposed studies can be anticipated to clarify the effects of estradiol and progesterone on the PI -signaling pathway in pregnant myometrium; thereby further elucidating the hormonal regulation of the onset of parturition.

磷脂酰肌醇（PI）信号通路在细胞凋亡中起着重要作用。在细胞内信号转导过程中，对各种激素和神经递质作出反应的非兴奋性细胞。我的实验室以前的研究表明，PI- 信号通路也发挥了重要作用，在产生细胞质钙振荡样现象，其基础是相位子宫肌层收缩磷酸肌醇特异性磷脂酶C（PI- 蛋白激酶C（PKC）和二酰基甘油脂肪酶（DAG-L），关键酶参与PI信号通路的酶，在妊娠中表达。大鼠子宫肌层;表达似乎在后一阶段被调节第三次怀孕虽然暂时指的是孕酮和雌二醇的上升发生在同一时期，在妊娠大鼠的妊娠中，负责这些信号转导酶的妊娠调节是不确定的。本研究旨在检验雌二醇和/或孕酮特异性地调节这些蛋白的活性和表达，妊娠大鼠子宫肌层中的关键信号转导酶。具体修订后的MMS应用程序是：1）评估妊娠的影响和类固醇激素对PI-PLC活性和表达的影响; 2）评价妊娠和类固醇激素对活动的影响， PKC表达; 3）评估妊娠和激素的影响激素对代谢DAG的酶活性的影响（即。DAG-L和二酰基甘油激酶（DAG-K））。这些研究报告将利用在正常子宫内膜组织中获得的大鼠子宫肌层组织进行妊娠，从孕鼠进行类固醇激素操作，来自假孕大鼠的体内和体外刺激的组织培养物类固醇激素预计这些拟议的研究将阐明雌二醇和孕酮对PI信号转导的影响妊娠子宫肌层中的激素途径;从而进一步阐明调节分娩的开始。