C/EBPβ is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma
C/EBPβ is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma
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DOI：
10.1073/pnas.0507261103
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发表时间：
2006-02-07
影响因子：
11.1
通讯作者：
Bagchi, MK
中科院分区：
文献类型：
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作者：
Mantena, SR;Kannan, A;Bagchi, MK
在妊娠早期，类固醇激素雌激素（E）和孕激素（P）通过及时控制子宫上皮和间质的增殖和分化来调节植入胚胎和子宫之间的一系列复杂的相互作用。为了确定控制这些功能的类固醇调节基因，我们在植入时对小鼠子宫组织进行了信使RNA分析。我们的分析表明，在胚泡附着时，转录因子CCAAT/增强子结合蛋白β（C/EBP β）的表达在妊娠子宫中被迅速诱导。C/EBP β的表达在妊娠的蜕膜化阶段进一步增加，并且定位于植入胚胎周围的增殖和蜕膜化的基质细胞。给予E或P卵巢切除的女性诱导C/EBP β在子宫上皮和间质中的表达，显示这些激素对该基因的双重调节。雌性C/EBP β缺失小鼠是不育的。因此，我们评估了这些小鼠子宫的类固醇激素依赖性反应。我们观察到E诱导的子宫上皮细胞增殖在C/EBP β缺乏的情况下明显受损。最引人注目的是，C/EBP β缺陷子宫对人工蜕膜刺激完全没有反应，表明这种转录因子在调节蜕膜化程序中起关键作用。进一步的分析显示，在C/EBP β-null子宫中，类固醇诱导的基质细胞增殖和分化存在缺陷。总的来说，我们的研究确定C/EBP β是小鼠子宫上皮和间质类固醇反应的关键介质。
During early pregnancy, steroid hormones estrogen (E) and progesterone (P) regulate a complex series of interactions between the implanting embryo and the uterus by controlling the proliferation and differentiation of uterine epithelium and stroma in a timely manner. To identify the steroid-regulated genes that control these functions, we performed messenger RNA profiling of mouse uterine tissues at the time of implantation. Our analysis revealed that the expression of the transcription factor CCAAT/enhancer-binding protein beta (C/EBP beta) is rapidly induced in the pregnant uterus at the time of blastocyst attachment. The expression of C/EBP beta increased further during the decidualization phase of pregnancy and was localized in the proliferating as well as the decidualized stromal cells surrounding the implanted embryo. Administration of E or P to ovariectornized females induced C/EBP beta expression in both uterine epithelium and stroma, showing a dual regulation of this gene by these hormones. The female C/EBP beta-null mice are infertile. We, therefore, assessed steroid-hormone-dependent responses in the uteri of these mice. We observed that E-induced proliferation of uterine epithelial cells is markedly compromised in the absence of C/EBP beta. Most strikingly, there was a complete lack of response of the C/EBP beta-deficient uteri to an artificial deciduogenic stimulus, indicating a critical role of this transcription factor in regulating the decidualization program. Further analysis revealed defects in steroid-induced stromal cell proliferation and differentiation in C/EBP beta-null uteri. Collectively, our studies established that C/EBP beta is a key mediator of steroid responsiveness of the epithelium and stroma in the mouse uterus.