Relaxin signalling in the endometrium and the regulation of early pregnancy

子宫内膜松弛素信号传导及早期妊娠的调节

• 批准号: nhmrc : 349502
• 负责人: Prof Richard Ivell
• 金额: $ 31.08万
• 依托单位: The University of Adelaide
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/relaxin-signalling-endometrium-early-pregnancy/96291
• 关键词: Relaxin; signalling; endometrium; regulation; early

Relaxin is a hormone, that is made in the ovary and the uterus, and plays a very important role in supporting the growth and development of the uterus so that the young embryo can implant properly. In fact, early pregnancy loss is associated with altered levels of relaxin in the blood. Very little is known about how relaxin works in the uterus. This project aims to address this important function, and makes use of cultured uterine cells prepared from tissues taken from women undergoing hysterectomy for fibroids or similar illnesses. When these cells are grown in culture, we can mimic in vitro many of the events that occur in early pregnancy, causing the cells to differentiate and grow just as they would in vivo. Relaxin appears to exert its important effects on these cells by causing the concentration of the second messenger cAMP in the so-called stromal cells to increase greatly and in a sustained manner. It is this cAMP which is then responsible for many of the changes which are essential for healthy pregnancy. A knowledge of the molecular mechanisms behind these effects would help us firstly to understand how the uterus becomes receptive to an implanting embryo, and may explain why some women lose their babies in early pregnancy, or develop some of the negative symptoms associated with placental development such as growth restriction and preeclampsia. Relaxin appears to stimulate cells through the mediation of a new type of cell surface receptor, called LGR7. Whilst structurally this receptor looks like those for many other hormones, belonging to the group of so-called G-protein coupled receptors, it does not behave like these in natural uterine cells. Instead it appears to make use of completely new signaling pathways inside the cells. This project aims to unravel and understand these new pathways, thus providing information not only of importance for diagnosis and treatment of early pregnancy problems, but also of relevance for all other similar receptors.

松弛素是一种激素，在卵巢和子宫中产生，在支持子宫的生长和发育方面起着非常重要的作用，以便年轻的胚胎能够正常植入。事实上，早孕丢失与血液中松弛素水平的改变有关。人们对松弛素在子宫中的作用机制知之甚少。该项目旨在解决这一重要功能，并利用从因子宫肌瘤或类似疾病接受子宫切除术的妇女的组织中制备的培养子宫细胞。当这些细胞在培养物中生长时，我们可以在体外模拟怀孕早期发生的许多事件，使细胞像在体内一样分化和生长。松弛素似乎通过引起所谓的基质细胞中第二信使cAMP的浓度大大增加并以持续的方式对这些细胞发挥其重要作用。正是这种cAMP负责许多对健康怀孕至关重要的变化。了解这些影响背后的分子机制将有助于我们首先了解子宫如何接受植入胚胎，并可能解释为什么有些妇女在怀孕早期失去婴儿，或出现一些与胎盘发育相关的阴性症状，如生长受限和先兆子痫。松弛素似乎通过一种新型的细胞表面受体LGR 7来刺激细胞。虽然在结构上，这种受体看起来像许多其他激素的受体，属于所谓的G蛋白偶联受体，但它在天然子宫细胞中的行为与这些受体不同。相反，它似乎利用了细胞内全新的信号通路。该项目旨在解开和了解这些新的途径，从而提供信息，不仅对诊断和治疗早孕问题的重要性，而且对所有其他类似受体的相关性。