CELLULAR MECHANISMS IN UTERINE PROSTAGLANDIN SYNTHESIS

子宫前列腺素(PGs)在着床过程中起着至关重要的作用， 分娩、黄体溶解和母亲对怀孕的认可。然而， 调节子宫合成前列腺素的因素还知之甚少。这个 本提案中描述的实验的目标是 描述调节这种合成的细胞内机制。 催产素刺激子宫组织合成前列腺素。这个 所描述的实验有两个具体目的。第一个是审查 磷脂酶C在介导血管紧张素转换酶刺激效应中的作用 催产素对PGs子宫合成的影响。随后的实验将是 以确定各种完整的膜蛋白如何相互作用 将催产素受体与磷脂酶C酶联系起来。这 信息将提供一个起点，从这里研究不同的 荷尔蒙和其他药物改变催产素刺激的能力 磷脂酶C的活性第二个具体目标是确定如何 细胞内第二信使(即cAMP、二酰甘油、肌醇 三磷酸盐，钙离子)调节子宫合成PGF2a。曾经很重要 确定了第二个信使，将进行实验以 表征介导第二种蛋白的特定调节蛋白 信使效应(即蛋白激酶、钙调蛋白)及其靶点 它们的活性(即脂皮质素、磷脂酶A2、环氧合酶)。 在我们对这些机制的理解上的改进有可能 用于产科、避孕和不孕不育的治疗 以及在生产食物的牲畜的繁殖管理方面。

Uterine prostaglandins (PGs) play an essential role in implantation, parturition, luteolysis and maternal recognition of pregnancy. Yet, the factors regulating uterine synthesis of PGs are poorly understood. The objective of the experiments described in this proposal is to characterize the intracellular mechanisms which regulate this synthesis. Oxytocin stimulates synthesis of PGs from uterine tissue. The experiments described have two specific aims. The first is to examine the role of phospholipase C in mediating the stimulatory effect of oxytocin on uterine synthesis of PGs. Subsequent experiments will be conducted to determine how various integral membrane proteins interact to link the oxytocin receptor to the phospholipase C enzyme. This information will provide a starting point from which to study how various hormones and other agents modify the ability of oxytocin to stimulate activity of phospholipase C. The second specific aim is to determine how intracellular second messengers (i.e. cAMP, diacylglycerol, inositol triphosphate, Ca++) regulate uterine synthesis of PGF 2a. Once important second messengers are identified, experiments will be conducted to characterize the specific regulatory proteins which mediate the second messenger effects (i.e. protein kinases, calmodulin) and the targets of their activity (i.e. lipocortin, phospholipase A2, cyclooxygenase). Improvements in our understanding of these mechanisms has the potential for application in obstetrics, contraception and treatment of infertility and in the reproductive management of food producing livestock.