REGULATION OF MYOMETRIAL CYCLASE ISOTYPE EXPRESSION

子宫张力正常变化的潜在机制不是很好 明白了。子宫张力增高的病理情况导致 早产和分娩期间子宫张力过高等情况 止痛药。一种被提出的子宫高张力的机制涉及急性 儿茶酚胺水平降低，但相关的子宫肌层信号 转导途径尚未完全阐明。最多的 产生子宫收缩和松弛的重要途径是 催产素(OT)和β-肾上腺素能受体(β-AR)介导 小路。我们的目标是了解这两者之间的交叉调节 妊娠对非妊娠子宫肌层的影响 交叉监管，以及交叉监管如何影响对变化的反应 在BetaAR活动中。初步结果显示慢性催产素 预处理抑制基础和刺激的腺苷环化酶(AC) 体内和体外活性。我们假设催产素诱导 AC水平的刺激性AG通路功能障碍导致导联 到子宫高张，因为β-AR输入被撤回。我们会研究 培养孕鼠和非孕大鼠及人子宫肌层细胞 用催产素进行预处理。为了确定交叉调节的机制，我们 将测量BetaAR和OT受体的数量和亲和力，以及AC 活动。为了确定AC的特定亚型的作用，我们将 确定所涉及的亚型的存在和数量 在下调AG的监管方面。为了进一步发展体内的模型 响应，我们将描述非妊娠和非妊娠的培养细胞 怀孕的大鼠和人类受试者。交叉监管作为一种 子宫活动亢进的常见机制将导致预防 胎儿窘迫和早产，从而减少了 不必要的剖腹产。这将带来更好的护理 母亲和孩子，以及降低分娩费用和 早产儿。

Mechanisms underlying normal changes in uterine tone are not well understood. Pathological situations of increased uterine tone lead to conditions such as preterm labor and uterine hypertonus during labor analgesia. A proposed mechanism of uterine hypertonus involves acute decreases in catecholamine levels, but the relevant myometrial signal transducing pathways have not been fully elucidated. The most important pathways producing uterine contraction and relaxation are the oxytocin (OT) and the beta adrenergic receptor (betaAR)-mediated pathways. Our goal is to understand crossregulation between these two pathways in nonpregnant myometrium, how pregnancy affects crossregulation, and how crossregulation affects responses to changes in betaAR activity. Preliminary results show that chronic OT pretreatment inhibits basal and stimulated adenylyl cyclase (AC) activity in vivo and in vitro. We hypothesize that OT-induced dysfunction of the stimulatory AG pathway, at the level of AC, leads to uterine hypertonus as betaAR input is withdrawn. We will study cultured pregnant and nonpregnant rat and human myometrial cells pretreated with OT. To identify the mechanism of crossregulation, we will measure numbers and affinities of betaAR and OT receptors, and AC activity. To identify the role of specific isoforms of AC, we will determine presence and quantities of mRNA for those isoforms involved in the down-regulation of AG. To further develop a model of in vivo responses, we will characterize cultured cells from nonpregnant and pregnant rats and human subjects. Knowledge of crossregulation as a common mechanism of uterine hyperactivity will lead to prevention of fetal distress and preterm labor, thus reducing the number of unnecessary cesarean sections. This will result in improved care of both the mother and child and to decreased costs of childbirth and prematurity.