Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus.
Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus.
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DOI：
10.1210/mend.9.6.8592515
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发表时间：
1995-06
影响因子：
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通讯作者：
S. Das;I. Chakraborty;B. Paria;Xiaohong Wang;G. Plowman;S. Dey
中科院分区：
文献类型：
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作者：
S. Das;I. Chakraborty;B. Paria;Xiaohong Wang;G. Plowman;S. Dey
胚泡的激活状态和子宫向接受状态的分化之间的同步性对于植入过程是必不可少的。这个过程是由孕酮（P4）和雌激素指导的。P4分化子宫，使雌激素启动植入的机制尚不清楚，但可能涉及生长和分化因子的局部诱导。我们已经克隆了小鼠双调蛋白（AR）基因，一个新发现的表皮生长因子家族的成员，并证明其表达是approximation特异性和P4调节小鼠子宫。在妊娠第4天，整个子宫上皮细胞的AR mRNA水平出现短暂的激增。随着第4天胚泡附着的开始，AR mRNA仅在胚泡部位的腔上皮中积累。因此，AR表达首先与P4水平升高相关，然后与附着反应相关。AR mRNA在卵巢切除子宫中仅由P4快速诱导，而RU-486（一种P4受体拮抗剂）可消除这种诱导，这表明该子宫基因受P4调节。AR似乎表现出优先磷酸化的表皮生长因子受体在子宫的囊胚。这是第一次报告的P4调节子宫上皮细胞生长因子，与上皮细胞分化在植入过程中。AR在着床中的相关性通过其在妊娠第4天子宫中的下调进一步证明，其中子宫容受性和着床在第3天被雌激素或RU-486处理破坏。这些结果进一步表明AR基因的表达可以作为子宫着床接受状态的分子标记。
A synchrony between the activated state of the blastocyst and differentiation of the uterus to the receptive state is essential to the process of implantation. This process is directed by progesterone (P4) and estrogen. The mechanism by which P4 differentiates the uterus, enabling estrogen to initiate implantation, is unknown but likely to involve localized induction of growth and differentiation factors. We have cloned the murine amphiregulin (AR) gene, a newly discovered member of the epidermal growth factor family, and demonstrate that its expression is implantation-specific and P4-regulated in the mouse uterus. A transient surge in AR mRNA levels occurred throughout the uterine epithelium on day 4 of pregnancy. With the onset of blastocyst attachment late on day 4, AR mRNA accumulated in the luminal epithelium exclusively at the sites of blastocysts. Thus, AR expression correlated first with rising P4 levels and then with the attachment reaction. The rapid induction of AR mRNA in the ovariectomized uterus only by P4 and abrogation of this induction by RU-486 (a P4 receptor antagonist) suggest that this uterine gene is regulated by P4. AR appeared to exhibit preferential phosphorylation of epidermal growth factor receptor in the uterus over that in the blastocyst. This is a first report of a P4-regulated uterine epithelial cell growth factor that is associated with epithelial cell differentiation during implantation. The association of AR in implantation is further documented by its down-regulation in the day 4 pregnant uterus in which uterine receptivity and implantation were disrupted by estrogen or RU-486 treatment on day 3. These results further indicate that the expression of the AR gene could serve as a molecular marker for the receptive state of the uterus for implantation.