RELAXIN: BIOCHEMICAL AND PHYSIOLOGICAL STUDIES

在人类和其他哺乳动物的妊娠晚期， 宫颈结缔组织的稠度因此软化，从而能够 宫颈扩张和胎儿快速分娩。 在情况下 足月自然分娩或诱导分娩困难时， 硬而无弹性的子宫颈可能是并发症的根源。 的 激素松弛素是一种有效的宫颈软化剂 在妇女和家畜中具有临床应用的潜力。 关于使用松弛素作为软化剂的明智决定 药物将在很大程度上取决于其作用的基础研究 人类以外的物种。 主要长期目标 该应用的目的是为了更好地理解，在分子 水平，松弛素通过影响的机制 结缔组织，促进孕妇子宫颈软化 老鼠。 具体目标是识别、隔离和 对其合成受刺激的蛋白聚糖进行特征化 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。 大鼠将在第9天被切除卵巢 怀孕并随后接受激素替代治疗 黄体酮和雌激素的生理水平——有或没有 松弛素。 宫颈将在怀孕后期（第 22 天）采集。 我们不仅要努力确定松弛素的作用 对从完整大鼠获得的整个宫颈（体内研究）但是 也在宫颈组织外植体和松弛素原代培养物上 反应性宫颈细胞（体外研究）。 的影响 细胞和细胞外宫颈成分上的松弛素将 可以在光学和电子显微镜水平上确定。 至 为了实现这一目标，单克隆被动神经化 将使用针对大鼠松弛素的特异性抗体来剥夺 妊娠大鼠下半年内源性松弛素 怀孕。 该应用程序的第二个目标是确定 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。 具体目标 将确定剥夺内源性的后果 用单克隆抗体被动中和松弛素后的松弛素 大鼠松弛素特异性抗体对生长和成分的影响 子宫角的生长和活力 怀孕后期的胎儿。

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.