PARACRINE REGULATION OF INTRAUTERINE PROSTAGLANDIN PRODUCTION

宫内前列腺素产生的旁分泌调节

• 批准号: 3741758
• 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/3741758
• 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.

分娩的过程使子宫精确地收缩 方式和宫颈扩张效率高，导致安全 婴儿的分娩。然而，这一过程往往因以下原因而变得复杂 偏离正常标准，可能导致早产，或 足月劳动效率低下，婴儿发病率和死亡率增加。 子宫收缩力和宫颈的主要控制因素 扩张症被认为是前列腺素。与人类的研究 组织和来自实验动物的组织已经证明 羊膜和蜕膜是前列腺素和催产素的来源， 前列腺素和催产素相互作用，促进彼此的分泌。 类固醇激素被认为是调节这种相互作用的重要因素。 通过外推其他物种的催产素和前列腺素 以及使用人体组织的初步证据。然而，没有 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。这种旁分泌相互作用很可能是受控制的 通过：1)激素对宫内催产素和前列腺素的调节 受体；2)催产素和前列腺素的特异性分泌 尤其是通过羊膜和蜕膜；以及3)正反馈循环， 导致催产素和前列腺素分泌增加。以前的研究 已证明胎龄对这些因素有影响； 然而，没有直接证据表明宫内催产素和 前列腺素的动态受类固醇的调节。皮质类固醇有 与人体前列腺素分泌的调节有关 羊膜。羊膜具有高亲和力的糖皮质激素受体，羊膜PGE2 分娩时产量增加，雌二醇促进蜕膜 前列腺素生产。蜕膜细胞上存在催产素受体 以及羊膜上皮细胞。蜕膜是主要的来源。 前列腺素F2pha，前列腺素在分娩时增加，雌二醇 促进蜕膜前列腺素的产生。这篇文章中概述的研究 GRANT用于确定皮质类固醇和催产素是否 羊膜前列腺素E_2分泌的重要调节因子以及雌激素和 孕酮对蜕膜中PGF2α释放的影响 添加催产素的影响。我们会在晚些时候收集羊膜和蜕膜 怀孕的恒河猴，并将这些细胞置于培养中。到时候我们会的 操纵培养中的类固醇环境，以确定如何 不同类固醇和类固醇组合对前列腺素的影响 分泌物。最后，我们将在培养基中加入催产素来确定 催产素是否可以控制前列腺素的分泌以及类固醇如何辅助 这一过程。前列腺素将通过特定的EIA进行测定。数据 收集将增加我们对灵长类分娩的知识 恒河猴是主要的动物模型。