MODULATION OF THE PI-PATHWAY IN PREGNANT MYOMETRIUM

磷脂酰肌醇(PI)信号通路起着至关重要的作用 在发生在细胞内的信号转导事件期间 对各种激素和神经递质作出反应的不可兴奋的细胞。 我的实验室之前的研究已经证明，PI- 信号通路也在细菌的产生过程中发挥着重要作用。 细胞内钙振荡样现象是时相的基础 子宫肌层收缩。磷脂酶C(PI-C) PLC)、蛋白激酶C(PKC)和二酰基甘油脂肪酶(DAG-L)，关键 参与PI信号通路的酶在怀孕期间表达 大鼠子宫肌层；在后者过程中似乎受到调节的表达 怀孕的第三个月。尽管临时改装了一下，以适应 黄体酮和雌二醇的升高发生在同一时期 在怀孕的大鼠中，负责 这些信号转导酶在妊娠中的调节尚不明确。 这项研究建议检验这样一种假设，即雌激素和/或 黄体酮专门调节这些基因的活性和表达。 妊娠大鼠子宫肌层中的关键信号转导酶。具体的 修订后的应用程序的MMS包括：1)评估妊娠影响 和类固醇激素对PI-PLC活性和表达的影响 妊娠和类固醇激素对其活性和功能的影响 PKC的表达，以及3)评估妊娠和类固醇的影响 激素对代谢失活DAG的酶活性的影响 (即DAG-L和二甘油酸激酶(DAG-K))。这些研究将是 利用正常情况下获取的大鼠子宫肌层组织进行手术 妊娠，从怀孕的大鼠接受类固醇激素操作 假孕大鼠的活体和体外刺激的组织培养 用类固醇激素。这些拟议的研究可以预期 阐明雌二醇和孕酮对PI信号转导的影响 在妊娠子宫肌层中的途径；从而进一步阐明激素 对分娩开始时间的规定。

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.