Molecular regulation of CRH gene expression in the human placenta

人胎盘CRH基因表达的分子调控

• 批准号: nhmrc : 141726
• 负责人: Prof Richard Nicholson
• 金额: $ 4.69万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/molecular-regulation-crh-human-placenta/78351
• 关键词: Molecular; regulation; CRH; gene; expression

Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely the rise in CRH production occurs earlier and more rapidly, while in women who deliver late the rise occurs more slowly. This work has led to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done by examining the DNA sequences involved in controlling the CRH gene and by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and preterm birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be developed.

大约 70% 的婴儿死亡是由早产造成的。 6-10% 的妊娠发生早产，并且这一比例在过去 30 年里没有下降。这主要是因为我们仍然不知道如何控制正常和早产。了解人类怀孕的生理学是开发检测和预防早产方法的关键一步。我们的研究小组已经证明了胎盘中激素（促肾上腺皮质激素释放激素，CRH）的产生与婴儿在母亲体内的时间长度之间存在联系。在早产的女性中，CRH 产生的增加发生得更早且更快，而在晚产的女性中，CRH 的增加发生得更慢。这项工作提出了生物钟的概念，它决定了胎儿在出生前由母亲携带的时间长度，其中胎盘中 CRH 的产生起着核心作用。我们一直在研究胎盘细胞中CRH基因是如何控制的。我们发现 CRH 基因 DNA 中的一些区域在控制胎盘产生 CRH 的量方面发挥着重要作用。该项目中描述的实验将确定控制人类胎盘中 CRH 产生的分子机制。这将通过检查涉及控制 CRH 基因的 DNA 序列以及识别实际执行调节功能（导致胎盘产生的 CRH 量增加或减少）的蛋白质来完成。这些重要信息将帮助我们更好地了解如何控制正常和早产，并根据这些知识开发出检测和预防早产的新方法。