RELAXIN: BIOCHEMICAL AND PHYSIOLOGICAL STUDIES

在人类和其他哺乳动物的妊娠晚期， 颈部结缔组织的稠度因此而变软，从而使 宫颈扩张和胎儿的快速分娩。在案件中 难于自然分娩或足月引产， 硬而无弹性的宫颈可能是并发症的来源之一。这个 激素松弛素是一种有效的宫颈软化剂， 在妇女和家畜中的临床应用潜力。 关于使用松弛素来软化的明智决定 助剂将在很大程度上取决于对其影响的基础研究 人类以外的物种。主要的长期目标是 这一应用的目的是更好地理解分子 水平，松弛的机制(S)，通过作用于 结缔组织，促进孕妇宫颈软化 老鼠。具体目标将是识别、隔离和 鉴定其合成受以下刺激的蛋白多糖 放松药。此外，松弛素对关键酶的影响 参与宫颈胶原的合成和降解 将会被确定。大鼠于术后第9天摘除卵巢 怀孕后接受激素替代治疗 黄体酮和雌激素的生理水平--有无 放松药。子宫颈将在怀孕后期(第22天)采集。 将做出重大努力来确定松弛素的效果，不仅是 取自完整大鼠的整个宫颈(活体研究)，但 宫颈组织外植体和松弛素的原代培养- 反应性宫颈细胞(体外研究)。的影响 松弛素对宫颈细胞和细胞外部分的作用 在光学和电子显微镜水平上进行测定。至 为了达到这个目的，用单克隆化被动神经化 针对大鼠松弛素的抗体将被用来剥夺 年下半年孕鼠内源性松弛素值 怀孕了。此应用程序的第二个目标是确定 被广泛接受(但未经证实)的假设是否 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 照顾发育中的胎儿是正确的。特殊的目标 将决定剥夺内源性神经营养物质的后果 松弛素与单抗被动中和后的松弛素 大鼠松弛素特异性抗体对其生长和组成的影响 以及子宫角的生长和活力 妊娠晚期的胎儿。

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.