Sex Steroid Hormones and Calcitonin Gene-Related Peptide

描述（由申请人提供）：平滑肌松弛剂分子是 与妊娠期间血管适应的调节有关， 正常的子宫胎盘功能和胎儿生长。我们的长期目标是 研究是为了确定有效的平滑肌松弛剂降钙素的作用， 基因相关肽（CGRP）在这些血管适应和子宫胎盘 功能在上一个资助期，我们发现， CGRP和CGRP的血管舒张作用在妊娠期间上调， 性类固醇激素的影响然而，CGRP诱导血管舒张的机制 以及CGRP参与子宫和胎盘血流 规则是未知的。因此，本申请的总体目标是 探讨降钙素基因相关肽（CGRP）舒张肠系膜动脉的机制 并评估CGRP在大鼠子宫胎盘血流中的参与。 有待检验的假设是：1）CGRP诱导的肠系膜淋巴细胞增殖增加， 妊娠期间动脉舒张是由于CGRP表达升高 受体成分，降钙素受体样受体（CRLR）和受体 信号转导修饰蛋白（RAMP1）及其受体后信号转导，和2） CGRP参与子宫胎盘血流的调节， 增长提出了三个具体目标。具体目标1：表征CGRP 受体和受体后信号在肠系膜动脉和描述 大鼠妊娠期间受体的调节和性类固醇的作用 荷尔蒙我们将测量CRLR和RAMP1的变化， 和肠系膜动脉舒张，并评估CGRP诱导的血液 在整个妊娠期流动，并评估其调节性类固醇激素。 具体目的2：检测CGRP对子宫动脉的舒张作用 并评估这些影响是否受怀孕和性类固醇的调节 荷尔蒙我们将测量CRLR、RAMP1和受体后信号传导的变化。 和子宫动脉舒张，并评估CGRP诱导的整个血流 妊娠和类固醇激素的调节。具体目标3：调查 CGRP在胎盘血流中的作用。我们将测量CRLR的变化， 妊娠晚期胎盘RAMP1和CGRP结合及其意义 性甾体激素影响及CGRP诱导的血流量评估 胎盘这些研究将有助于评估CGRP参与血管 适应和胎儿生长在怀孕期间，奠定了基础， 评估CGRP在妊娠期的治疗价值。

DESCRIPTION (provided by applicant): Smooth muscle relaxant molecules are implicated in the regulation of vascular adaptations during pregnancy and in normal uteroplacental function and fetal growth. The long-term goal of our research is to define the role of potent, smooth muscle relaxant, calcitonin gene-related peptide (CGRP) in these vascular adaptations and uteroplacental function. In the previous funding period, we found that both the expression of CGRP and the vasodilatory action of CGRP are upregulated during pregnancy and by sex-steroid hormones. However, the mechanisms of CGRP-induced vasodilation as well as the involvement of CGRP in uterine and placental blood flow regulation are not known. Thus, the overall goal of this application is to determine the mechanisms of CGRP-induced vasorelaxation of mesenteric artery and assess the involvement of CGRP in uteroplacental blood flow in the rat. Hypotheses to be tested are: 1) that the increased CGRP-induced mesenteric artery relaxation during pregnancy is due to elevated expression of CGRP receptor components, caicitonin receptor-like receptor (CRLR) and receptor signaling modifying protein (RAMP1), and their post-receptor signaling, and 2) CGRP is involved in the regulation of uteroplacental blood flow and fetal growth. Three specific aims are proposed. Specific aim 1: to characterize CGRP receptors and post-receptor signaling in the mesenteric artery and describe the regulation of the receptors during rat pregnancy and by the sex-steroid hormones. We will measure changes in CRLR and RAMP1, post-receptor signaling and arterial relaxation of mesenteric artery, and assess CGRP-induced blood flow throughout gestation and assess their regulation by sex-steroid hormones. Specific aim 2: to examine the vasodilatory effects of CGRP on uterine artery and assess if these effects are regulated by pregnancy and sex-steroid hormones. We will measure changes in CRLR, RAMP1 and post-receptor signaling and relaxation of uterine artery, and assess CGRP-induced blood flow throughout gestation and regulation by steroid hormones. Specific aim 3: to investigate the role of CGRP in placental blood flow. We will measure changes in CRLR, RAMP1 and CGRP binding in placenta throughout late gestation and their influence by sex-steroid hormones and assess CGRP-induced blood flow through placenta. These studies would help assess the involvement of CGRP in vascular adaptations and in fetal growth during pregnancy and lay a foundation for assessing therapeutic value of CGRP in pregnancy.