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.

分娩过程允许子宫准确收缩 方式和子宫颈有效扩张，导致安全 婴儿的分娩。但是，这个过程通常会因 与规范的偏差可能导致早产或 婴儿发病率和死亡率增加，劳动效率低下。 子宫收缩性和宫颈的主要控制因素 扩张被认为是前列腺素。人类的研究 组织和实验动物的组织表明 羊膜和Decidua是前列腺素和催产素的来源， 前列腺素和催产素相互作用以增强彼此的分泌。 类固醇激素被认为对调节相互作用很重要 催产素和前列腺素是通过从其他物种中推断出来的 以及使用人体组织的初步证据。但是，没有 与宫内组织中催产素和前列腺素分泌有关的数据 在非人类灵长类动物中。这种旁分泌相互作用可能受到控制 通过：1）宫内催产素和前列腺素的类固醇调节 受体； 2）催产素和前列腺素的特定分泌 特别是由羊膜和Decidua进行的； 3）一个积极的反馈循环 导致催产素和前列腺素分泌增加。先前的研究 已经证明对这些因素有妊娠年龄的影响； 但是，没有直接的证据表明宫内催产素和 前列腺素动力学受类固醇调节。皮质类固醇具有 与人类的前列腺素分泌有关 羊膜。羊膜具有高亲和力糖皮质激素受体，羊膜PGE2 劳动力和雌二醇的生产增加可增强决法 前列腺素生产。催产素受体存在于codidual细胞上 以及羊膜上皮细胞。 Decidua是 PGF2Alpha，前列腺素的产生在劳动力和雌二醇时增加 增强depotalis的前列腺素生产。其中概述了 授予旨在确定皮质类固醇和催产素是否为 羊膜PGE2分泌的重要调节剂以及雌激素和如何 孕酮影响有或没有 添加催产素的影响。我们将从迟到 妊娠颗粒猕猴，并将这些细胞放在培养物中。然后我们会 操纵文化中的类固醇环境，以确定如何 各种类固醇和类固醇的组合会影响前列腺素 分泌。最后，我们将在培养基中添加催产素以确定 如果催产素可以控制前列腺素的分泌以及类固醇如何辅助 这个过程。前列腺素将由特定的EIA测量。数据 收集到的将增加我们对灵长类动物的了解 恒河猴是主要动物模型。