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）信号途径起着至关重要的作用在细胞内信号转导事件中发生不可响应的细胞响应各种激素和神经递质。我的Lahoratory的先前研究表明，信号通路在生成过程中也起着重要作用基于阶段的胞质钙振荡样现象肌层收缩。磷酸肌醇特异性磷脂酶C（PI- PLC），蛋白激酶C（PKC）和二酰基甘油脂肪酶（DAG-L），钥匙参与PI信号途径的酶在怀孕中表达大鼠子宫骨肌；在后者期间似乎已调制的表达妊娠的第三。虽然暂时性地归结为跌倒孕酮和雌二醇的升高发生在同一时期怀孕大鼠的妊娠，负责的特定事件这些信号转导酶的妊娠调节不确定。这项研究提议检验雌二醇和/或的假设孕酮明确调节这些活性和表达怀孕大鼠子宫内矩阵中的键信号转导酶。具体此修订应用程序的MMS是：1）评估妊娠的影响和类固醇激素对PI-PLC的活性和表达，2）评估妊娠和类固醇激素对活动的影响 PKC的表达和3）评估妊娠和类固醇的影响激素对代谢灭活dag的活性的激素（即DAG-L和二酰基甘油激酶（DAG-K））。这些研究将是利用正常情况下获得的大鼠肌层组织进行妊娠，来自接受类固醇激素操纵的怀孕大鼠体内的体内大鼠和组织培养物在体外刺激与类固醇激素。这些提出的研究可以预期阐明雌二醇和孕酮对PI信号的影响孕妇子宫肌的途径；从而进一步阐明激素调节分娩的发作。