New insights into the molecular endocrinology of parturition
New insights into the molecular endocrinology of parturition
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DOI：
10.1016/j.jsbmb.2004.12.027
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发表时间：
2005-02-01
影响因子：
4.1
通讯作者：
Condon, JC
中科院分区：
文献类型：
--
作者：
Mendelson, CR;Condon, JC
导致分娩开始的信号仍然是一个谜。我们假设，在人类和其他哺乳动物中，子宫静止是通过增加孕激素受体（PR）转录活性来维持的，自发分娩是由一系列对PR功能产生负面影响的生化事件引发或促进的。在最近的研究中，我们获得了令人信服的证据表明，胎儿通过分泌主要的肺表面活性蛋白SP-A进入羊水来发出分娩的信号。SP-A表达在胎肺中受到发育调节，并在近期（小鼠妊娠后17天[dpc]）以高浓度分泌到羊水中。我们发现，在妊娠15 d时将外源性SP-A注入小鼠羊水中可引起早产。SP-A在体外激活羊水巨噬细胞表达核因子κ B（NF-κ B）和白细胞介素-1 β（IL-1 β）。这些巨噬细胞是胎儿来源的，迁移到妊娠子宫引起炎症反应和子宫NF-κ B活性增加。我们认为母体子宫内NF-κ B的增加直接增加了促进子宫收缩的基因的表达，并对PR维持子宫静止的能力产生负面影响，从而促进分娩的发生。因此，我们的研究结果表明，SP-A分泌到羊水中的成熟胎肺作为一种激素的分娩。(c)2004爱思唯尔有限公司保留所有权利。
The signals that lead to the initiation of parturition have remained a mystery. We postulate that in humans and other mammals, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, and spontaneous labor is initiated or facilitated by a concerted series of biochemical events that negatively impact PR function. In recent studies, we have obtained compelling evidence to suggest that the fetus signals the initiation of labor by secretion into amniotic fluid of major lung surfactant protein, SP-A. SP-A expression is developmentally regulated in fetal lung and is secreted into amniotic fluid in high concentrations near term (after 17 days postcoitum [dpc] in the mouse). We found that injection of exogenous SP-A into mouse amniotic fluid at 15 dpc caused preterm labor. SP-A activated amniotic fluid macrophages in vitro to express nuclear factor kappa B (NF-kappa B) and interleukin-1 beta (IL-1 beta). These macrophages, which are of fetal origin, migrate to the pregnant uterus causing an inflammatory response and increased uterine NF-kappa B activity. We suggest that the increase in NF-kappa B within the maternal uterus both directly increases expression of genes that promote uterine contractility and negatively impacts the capacity of the PR to maintain uterine quiescence, contributing to the onset of labor. Our findings, therefore, indicate that SP-A secreted into ammotic fluid by the maturing fetal lung serves as a hormone of parturition. (c) 2004 Elsevier Ltd. All rights reserved.