Progesterone regulation of the mammalian ortholog of methylcitrate dehydratase (immune response gene 1) in the uterine epithelium during implantation through the protein kinase C pathway
Progesterone regulation of the mammalian ortholog of methylcitrate dehydratase (immune response gene 1) in the uterine epithelium during implantation through the protein kinase C pathway
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DOI：
10.1210/me.2003-0207
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发表时间：
2003-11-01
影响因子：
--
通讯作者：
Pollard, JW
中科院分区：
文献类型：
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作者：
Chen, B;Zhang, DM;Pollard, JW
着床需要胚泡发育和性类固醇激素调节的子宫分化之间的协调。在这些激素的影响下，子宫腔上皮变得易于接受孵化胚泡的附着。在这项研究中，我们试图确定基因调节孕激素（P-4）在子宫上皮细胞。这导致了一种新的P-4调节基因的鉴定，该基因以前在脂多糖刺激的巨噬细胞中发现，称为免疫应答基因-1（Irg 1），并且是编码甲基柠檬酸酯酶的细菌基因的哺乳动物直系同源物。在成年小鼠中，Irg 1表达仅限于子宫腔上皮，仅在妊娠期间表达，峰值与着床一致。Irg 1 mRNA表达受P-4和雌二醇（E-2）的协同调节，但不受单独的E-2的调节。在巨噬细胞中，Irg 1通过蛋白激酶C（PKC）调节途径被脂多糖诱导。现在，我们证明，PKC途径是诱导在子宫上皮在植入的协同作用的P-4和E-2，是负责的激素诱导Irg 1。这些结果表明，PKC途径在着床窗口期间调节子宫腔上皮类固醇激素反应性中发挥重要作用，Irg 1将是该窗口的重要标志物，并可能在着床过程中发挥重要作用。
Implantation requires coordination between development of the blastocyst and the sex steroid hormone-regulated differentiation of the uterus. Under the influence of these hormones, the uterine luminal epithelium becomes receptive to attachment of the hatched blastocyst. In this study we sought to identify genes regulated by progesterone (P-4) in the uterine epithelium. This resulted in the identification of one novel P-4-regulated gene that had been previously found in lipopolysaccharide-stimulated macrophages and called immune response gene-1 (Irg1) and which is the mammalian ortholog of the bacterial gene encoding methylcitrate dehydratase. In adult mice Irg1 expression was limited to the uterine luminal epithelium where it is expressed only during pregnancy with a peak coinciding with implantation. Irg1 mRNA expression is regulated synergistically by P-4 and estradiol (E-2) but not by E-2 alone. In macrophages Irg1 is induced by lipopolysaccharide through a protein kinase C ( PKC)- regulated pathway. Now we demonstrate that the PKC pathway is induced in the uterine epithelium at implantation by the synergistic action of P-4 and E-2 and is responsible for the hormone induction of Irg1. These results suggest that the PKC pathway plays an important role in modulating steroid hormone responsiveness in the uterine luminal epithelium during the implantation window and that Irg1 will be an important marker of this window and may play an important role in implantation.