Sex Steroid Hormones and Calcitonin Gene-Related Peptide

性类固醇激素和降钙素基因相关肽

• 批准号: 6435750
• 负责人: CHANDRASEKHAR YALLAMPALLI
• 金额: $ 29.8万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-20 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6435750
• 关键词: RNA directed DNA polymerase; biological signal transduction; calcitonin gene related peptide; embryo /fetus; enzyme linked immunosorbent assay; female; gene induction /repression; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; mesenteric artery; muscle relaxants; placenta; pregnancy circulation; receptor expression; sex hormones; steroid hormone; tissue /cell culture; transfection /expression vector; uterus; vascular endothelium; vascular resistance; vasodilation; western blottings

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.

描述（由申请人提供）： 平滑肌松弛分子是 与妊娠期间和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 研究目的是确定强效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。在之前的资助期间，我们发现两者的表达都是 CGRP 及其血管舒张作用在怀孕期间和 通过性类固醇激素。然而，CGRP 诱导血管舒张的机制 以及 CGRP 参与子宫和胎盘血流 监管不详。因此，该应用程序的总体目标是 确定 CGRP 诱导肠系膜动脉血管舒张的机制 并评估 CGRP 对大鼠子宫胎盘血流的影响。 要检验的假设是：1）CGRP 诱导的肠系膜增加 妊娠期间动脉松弛是由于 CGRP 表达升高所致 受体成分，降钙素受体样受体（CRLR）和受体 信号修饰蛋白 (RAMP1) 及其受体后信号传导，以及 2) CGRP参与子宫胎盘血流和胎儿的调节 生长。提出了三个具体目标。具体目标 1：表征 CGRP 肠系膜动脉中的受体和受体后信号传导并描述 大鼠怀孕期间受体的调节以及性类固醇的调节 荷尔蒙。我们将测量 CRLR 和 RAMP1、受体后信号传导的变化 和肠系膜动脉的动脉舒张，并评估 CGRP 诱导的血液 整个妊娠期的流动并评估性类固醇激素对其的调节。 具体目标2：考察CGRP对子宫动脉的舒血管作用 并评估这些影响是否受到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 和舒张子宫动脉，并评估 CGRP 诱导的整个子宫血流 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， RAMP1 和 CGRP 在整个妊娠晚期胎盘中的结合及其 性类固醇激素的影响并评估 CGRP 诱导的血流 胎盘。这些研究将有助于评估 CGRP 在血管生成中的参与情况。 怀孕期间的适应和胎儿的生长发育奠定了基础 评估 CGRP 在妊娠中的治疗价值。