PARACRINE REGULATION OF INTRAUTERINE PROSTAGLANDIN PRODUCTION

宫内前列腺素产生的旁分泌调节

• 批准号: 3763937
• 负责人: GEORGE J HALUSKA
• 金额: --
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3763937
• 关键词: Macaca mulatta; amnion; birth; corticosteroids; decidua; estradiol; estrogens; glucocorticoids; hormone regulation /control mechanism; oxytocin; paracrine; progesterone; prostaglandins; secretion; tissue /cell culture

The process of parturition allows the uterus to contract in a precise manner and the cervix to dilate efficiently, resulting in the safe delivery of the infant. This process, however, is often complicated by deviations from the norm which may result in preterm delivery, or inefficient labor at term with increased infant morbidity and mortality. Primary controlling factors of uterine contractility and cervical dilatation are thought to be the prostaglandins. Studies with human tissues and those from laboratory animals have demonstrated that the amnion and decidua are sources of prostaglandins and oxytocin and that prostaglandins and oxytocin interact to enhance each others secretion. Steroid hormones are thought to be important in regulating the interaction of oxytocin and prostaglandins through extrapolation from other species as well as preliminary evidence using human tissues. There is, however, no data relating oxytocin and prostaglandin secretion in intrauterine tissues in non-human primates. This paracrine interaction is likely controlled through: 1) steroid regulation of intrauterine oxytocin and prostaglandin receptors; 2) the specific secretIon of oxytocin and prostaglandins especially by the amnion and decidua; and 3) a positive feedback loop that leads to increased oxytocin and prostaglandin secretion. Previous studies have demonstrated that there is a gestational age effect on these factors; however, there is no direct evidence that intrauterine oxytocin and prostaglandin dynamics are regulated by steroids. Corticosteroids have been implicated in regulation of prostaglandin secretion from human amnion. The amnion has high affinity glucocorticoid receptors, amnion PGE2 production increases at labor and estradiol enhances decidual prostaglandin production. Oxytocin receptors are present on decidual cells as well as amnion epithelial cells. The decidua is the major source of PGF2alpha, prostaglandin production increases at labor, and estradiol enhances decidual prostaglandin production. The studies outlined in this grant are designed to determine if corticosteroids and oxytocin are important regulators of amnion PGE2 secretion and how estrogen and progesterone affect PGF2alpha release from decidua with and without the influence of added oxytocin. We will collect amnion and decidua from late gestation rhesus macaques and place these cells in culture. We will then manipulate the steroid environment in the cultures to determine how various steroids and combinations of steroids affect prostaglandin secretion. Finally, we will add oxytocin to the culture media to determine if oxytocin can control prostaglandin secretion and how steroids assist this process. Prostaglandins will be measured by specific EIA. The data collected will add to our knowledge of primate parturition for which the rhesus monkey is the primary animal model.

分娩的过程使子宫以精确的方式收缩， 的方式和宫颈扩张有效，导致安全 婴儿的分娩。然而，这一过程往往因 可能导致早产的标准偏差，或 分娩效率低下，婴儿发病率和死亡率增加。 子宫收缩力和宫颈病变的主要控制因素 膨胀被认为是类胡萝卜素。人类研究 组织和来自实验室动物的那些已经证明， 羊膜和蜕膜是胎盘素和催产素的来源， 前列腺素和催产素相互作用以增强彼此的分泌。 类固醇激素被认为是重要的调节相互作用 通过从其他物种的推断， 以及使用人体组织的初步证据。然而，没有 子宫内组织中催产素和前列腺素分泌的相关数据 在非人类灵长类动物中。这种旁分泌的相互作用很可能是由 通过：1）类固醇调节子宫内催产素和前列腺素 受体; 2）催产素和肾上腺素的特异性分泌 特别是通过羊膜和蜕膜;和3）正反馈回路， 导致催产素和前列腺素分泌增加。以前的研究 已经证明胎龄对这些因素有影响; 然而，没有直接证据表明子宫内催产素和 前列腺素动力学受类固醇调节。皮质类固醇 与调节人前列腺素分泌有关 羊膜羊膜具有高亲和力的糖皮质激素受体，羊膜PGE 2 生产增加在劳动和雌二醇增强蜕膜 前列腺素的产生催产素受体存在于蜕膜细胞上 以及羊膜上皮细胞。蜕膜是子宫内膜的主要来源， PGF 2 α，分娩时前列腺素产生增加，雌二醇 促进蜕膜前列腺素的产生。本文中概述的研究 补助金旨在确定皮质类固醇和催产素是否 羊膜PGE 2分泌的重要调节因子以及雌激素和 孕酮影响PGF 2 α从有和没有蜕膜释放 添加催产素的影响。晚采集羊膜及蜕膜 将这些细胞置于培养物中。然后我们将 操纵培养物中的类固醇环境以确定如何 各种类固醇和类固醇组合会影响前列腺素 分泌物最后，我们将催产素添加到培养基中，以确定 如果催产素可以控制前列腺素的分泌， 这个过程将通过特定EIA测量前列腺素。数据 收集的信息将增加我们对灵长类动物分娩的了解， 恒河猴是主要的动物模型。