Expression and steroid hormonal control of Muc-1 in the mouse uterus.
Expression and steroid hormonal control of Muc-1 in the mouse uterus.
复制标题
DOI：
10.1210/endo.136.8.7628404
复制
发表时间：
1995-08
期刊：
影响因子：
4.8
通讯作者：
G. A. Surveyor;S. Gendler;Lucy C. Pemberton;S. Das;I. Chakraborty;J. Julian;R. Pimental;C. Wegner-C.-W
中科院分区：
文献类型：
--
作者：
G. A. Surveyor;S. Gendler;Lucy C. Pemberton;S. Das;I. Chakraborty;J. Julian;R. Pimental;C. Wegner-C.-W
本实验室以前的研究表明，大M（r）粘蛋白糖蛋白是体外小鼠子宫上皮细胞的主要顶端分布成分。目前的研究表明，Muc-1代表小鼠子宫上皮细胞的顶部布置的粘蛋白糖蛋白之一，并且Muc-1蛋白和信使RNA（mRNA）的表达在围着床期小鼠子宫中由卵巢类固醇调节。在所有检查条件下，Muc-1表达仅限于子宫上皮细胞。MUC-1在动情前期和动情期表达较高，在动情间期表达降低。Muc-1蛋白和mRNA在妊娠第4天即胚泡附着之前下降到几乎检测不到的水平。相反，宫颈和阴道中的Muc-1表达在同一时期维持。通过卵巢切除建立小鼠延迟着床模型，并给予外源性孕酮（P）维持着床。通过向P-维持小鼠共注射起始剂量的17 β-雌二醇（E2）触发着床。P-维持小鼠子宫上皮中的Muc-1水平下降至与正常妊娠第4天观察到的水平相似的低水平。共注射E2并不改变Muc-1的表达，这表明Muc-1的下调是一个P主导的事件。这一点在卵巢切除的非妊娠小鼠中得到了证实，这些小鼠在注射E2 6 h后显示出Muc-1表达的刺激。E2刺激的Muc-1表达被纯抗雌激素ICI 164，384抑制。虽然P单独对Muc-1的表达没有影响，但它拮抗了E2的作用。在妊娠第3天注射抗孕激素RU 486（一种已知的着床抑制剂）可在第4天恢复Muc-1 mRNA的高水平表达，表明Muc-1的下调是P受体介导的。总的来说，这些数据表明，小鼠子宫上皮中的Muc-1表达强烈影响卵巢类固醇。提示Muc-1的缺失有助于子宫接受性状态的产生。
Previous studies from our laboratory established that large M(r) mucin glycoproteins are major apically disposed components of mouse uterine epithelial cells in vitro. The present studies demonstrate that Muc-1 represents one of the apically disposed mucin glycoproteins of mouse uterine epithelia, and that Muc-1 protein and messenger RNA (mRNA) expression are regulated in the periimplantation mouse uterus by ovarian steroids. Muc-1 expression is exclusive to the epithelial cells of the uterus under all conditions examined. Muc-1 expression is high in the proestrous and estrous stages and decreases during diestrous. Both Muc-1 protein and mRNA decline to barely detectable levels by day 4 of pregnancy, i.e. before the time of blastocyst attachment. In contrast, Muc-1 expression in the cervix and vagina is maintained during this same period. Delayed implantation was established in pregnant mice by ovariectomy and maintained by the administration of exogenous progesterone (P). Initiation of implantation was triggered by coinjection of P-maintained mice with a nidatory dose of 17 beta-estradiol (E2). Muc-1 levels in the uterine epithelia of P-maintained mice declined to low levels similar to those observed on day 4 of normal pregnancy. Coinjection of E2 did not alter Muc-1 expression, suggesting that down-regulation of Muc-1 is a P-dominated event. This was confirmed in ovariectomized nonpregnant mice, which displayed stimulation of Muc-1 expression after 6 h of E2 injection. E2-Stimulated Muc-1 expression was inhibited by the pure antiestrogen, ICI 164,384. Although P alone had no effect on Muc-1 expression, it antagonized the action of E2. Injection of pregnant mice with the antiprogestin, RU486, a known implantation inhibitor, on day 3 of pregnancy restored high level expression of Muc-1 mRNA on day 4, indicating that down-regulation of Muc-1 is P receptor mediated. Collectively, these data indicate that Muc-1 expression in mouse uterine epithelium is strongly influenced by ovarian steroids. It is suggested that the loss of Muc-1 contributes to generation of a receptive uterine state.