REGULATION OF EICOSANOID RECEPTORS IN MYOMETRIUM

早产是围产儿发病率和死亡率的最大原因。 每年36,000名婴儿死亡中有75%是由它直接造成的 在美国。二十烷基类(前列腺素)是一种有效的介体。 并参与子宫肌层收缩的发生和维持。 劳力。几种二十烷类受体已被克隆和测序 提供机会研究它们的表达和调控 整个妊娠和分娩时的子宫肌层。子宫肌层的收缩能力是 荷尔蒙受性类固醇雌激素和孕激素调节 可能改变子宫肌层对前列腺素的敏感性，即通过 也许改变了受体的表达。这项提议的目标是 目的：(1)鉴定子宫肌层中存在的二十烷基类受体(2) 确定它们的细胞定位(3)研究表达的个体发育 通过怀孕和分娩开始以及(4)检查荷尔蒙 对表达的调节。研究将主要使用怀孕的老鼠和 将采用几种荷尔蒙调节模型，这些模型要么诱导 在这个物种中早产或防止分娩的开始。平行 研究将在怀孕的人子宫肌层中进行，从四个 一组患者，足月分娩或非临产或早产 或者不是在分娩。为了实现这些目标，拟议的实验 将利用逆转录聚合酶链式反应，北方 斑点杂交和原位杂交。这些研究将提供新的数据 二十烷基类受体的表达与骨质疏松症发病的关系 子宫肌层收缩能力。归根结底，这些知识可能对 为宫缩提供了新的子宫选择方法。

Preterm labor is the largest cause of perinatal morbidity and mortality and is directly responsible for 75% of the 36,000 infant deaths per annum in the USA. Eicosanoids (Prostaglandins) are potent mediators of myometrial contractility and are involved in the onset and maintenance of labor. Several eicosanoid receptors have been cloned and sequenced offering opportunities to study their expression and regulation in myometrium throughout gestation and at labor. Myometrial contractility is hormonally regulated by the sex steroids estrogen and progesterone which may alter the sensitivity of myometrium to prostaglandins, i.e., by perhaps altering receptor expression. The objectives of this proposal are to: (1) identify the eicosanoid receptors present in myometrium (2) determine their cellular localization (3) study the ontogeny of expression through gestation and with the onset of labor and (4) examine the hormonal regulation of expression. Studies will primarily use the pregnant rat and will employ several models of hormonal manipulation that either induce preterm labor or prevent the onset of labor in this species. Parallel studies will be performed in pregnant human myometrium obtained from four groups of patients, at term either in or not in labor or preterm either in or not in labor. To achieve these objectives, the proposed experiments will utilize reverse transcription-polymerase chain reaction, northern blotting and in situ hybridization. These studies will provide novel data on the expression of eicosanoid receptors in relation to the onset of myometrial contractility. Ultimately, this knowledge may be beneficial in providing new uterine selective methods of tocolysis.