RELAXIN: BIOCHEMICAL AND PHYSIOLOGICAL STUDIES

放松：生化和生理学研究

• 批准号: 3310967
• 负责人: ORRIN David SHERWOOD
• 金额: $ 10.48万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3310967
• 关键词: birth; blood chemistry; cervix; collagen; connective tissue; electron microscopy; gel electrophoresis; genital secretion; gestational age; hormone receptor; hormone regulation /control mechanism; hybridomas; hypophysectomy; ion exchange chromatography; laboratory mouse; laboratory rat; luteinizing hormone; mammalian embryology; monoclonal antibody; ovariectomy; ovary; passive immunization; peptide hormone biosynthesis; pituitary gland; pregnancy; progesterone; protein degradation; proteoglycan; radioimmunoassay; relaxin

During late pregnancy in humans and other mammalian species, the consistency of cervical connective tissue softens thus, enabling cervical dilatation and rapid delivery of the fetus(es). In cases of difficult spontaneous delivery or induced delivery at term, a hard inelastic cervix may be a source of complications. The hormone relaxin is an effective cervical softening agent with potential for clinical application in women and domestic animals. Informed decisions concerning the use of relaxin as a softening agent will largely depend upon basic studies of its effects in species other than the human. The principal long-range objective of this application is to better understand, at the molecular level, the mechanism(s) whereby relaxin, through effects upon the connective tissue, promotes softening of the cervix in the pregnant rat. The specific aims will be to identify, isolate, and chazacterize proteoglycans whose synthesis is stimulated by relaxin. Additionally, the influence of relaxin on key enzymes involved with the synthesis and degradation of cervical collagen will be determined. Rats will be ovariectomized on day 9 of pregnancy and thereafter receive hormone replacement therapy with physiological levels of progesterone and estrogen--with and without relaxin. Cervices will be collected late in pregnancy (day 22). Major efforts will be made to determine relaxin's effects not only on entire cervices obtained from intact rats (in vivo studies) but also on cervical tissue explants and primary cultures of relaxin- responsive cervical cells (in vitro studies). The influence of relaxin on both cellular and extracellular cervical components will be determined at the light and electron microscope level. To accomplish this aim, passive neurralization with monoclonal antibodies specific for rat relaxin will be done to deprive pregnant rats of endogenous relaxin during the second half of pregnancy. A second objective of this application is to determine whether the widely held (but unsubstantiated) hypothesis that relaxin, through its effects upon growth and connective tissue remodeling of the rat uterine horns, plays an important role in accommodating the developing fetuses is correct. The speciiic aims will be to determine the consequences of deprivation of endogenous relaxin following passive neutralization of relaxin with monoclonal antibodies specific for rat relaxin on the growth and composition of the uterine horns as well as the growth and vitality of the fetuses during late pregnancy.

在人类和其他哺乳动物的妊娠晚期， 子宫颈结缔组织的一致性软化，从而使 宫颈扩张和胎儿快速分娩。 情况下 足月自然分娩或引产困难， 坚硬的无弹性宫颈可能是并发症的来源。 的 激素松弛素是一种有效宫颈软化剂， 在女性和家畜中的临床应用潜力。 关于使用松弛素作为软化剂的知情决定 代理将在很大程度上取决于其影响的基础研究， 人类以外的物种。 主要的长期目标 是为了更好地理解 水平，松弛素，通过影响 结缔组织，促进软化的子宫颈在怀孕 大鼠 具体目标是识别、分离和 其合成受以下刺激的沙杂菌蛋白聚糖 松弛素 此外，松弛素对关键酶的影响 参与宫颈胶原蛋白的合成和降解 将被确定。 将在第9天对大鼠进行卵巢切除术。 怀孕后接受激素替代治疗， 孕酮和雌激素的生理水平--有和没有 松弛素 将在妊娠后期（第22天）采集宫颈。 将作出重大努力，以确定松弛素的影响，不仅 对从完整大鼠获得的整个子宫颈（体内研究），但 还在宫颈组织外植体和松弛素的原代培养物上， 宫颈细胞（体外研究）。 的影响 细胞和细胞外宫颈成分上的松弛素将 在光学和电子显微镜水平上进行测定。 到 为了实现这一目标，使用单克隆抗体进行被动神经再生， 将使用大鼠松弛素特异性抗体， 孕鼠内源性松弛素在孕后期 怀孕 本申请的第二个目的是确定 是否广泛持有（但未经证实）的假设， 松弛素，通过其对生长和结缔组织的影响 大鼠子宫角的重塑，在 适应发育中的胎儿是正确的。 特殊的目标 将是确定剥夺内源性 松弛素在用单克隆抗体被动中和松弛素后 大鼠松弛素特异性抗体对生长和组成的影响 以及子宫角的生长和活力， 怀孕后期的胎儿。