Surveyor G A, Gendler S J, Pemberton L, Das S K, Chakraborty I, Julian J, Pimental R A, Wegner C C, Dey S K, Carson D D
Department of Biochemistry and Molecular Biology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Endocrinology. 1995 Aug;136(8):3639-47. doi: 10.1210/endo.136.8.7628404.
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.
我们实验室之前的研究表明，大分子质量（M(r)）黏蛋白糖蛋白是体外培养的小鼠子宫上皮细胞主要的顶端分布成分。目前的研究表明，Muc-1是小鼠子宫上皮顶端分布的黏蛋白糖蛋白之一，并且在植入前小鼠子宫中，Muc-1蛋白和信使核糖核酸（mRNA）的表达受卵巢类固醇调节。在所有检测条件下，Muc-1仅在子宫上皮细胞中表达。Muc-1在动情前期和动情期表达较高，在动情间期降低。到妊娠第4天，即胚泡着床前，Muc-1蛋白和mRNA均降至几乎检测不到的水平。相比之下，同期宫颈和阴道中的Muc-1表达维持不变。通过对妊娠小鼠进行卵巢切除建立延迟着床，并通过给予外源性孕酮（P）维持。通过向用P维持的小鼠注射着床剂量的17β-雌二醇（E2）触发着床启动。用P维持的小鼠子宫上皮中的Muc-1水平降至与正常妊娠第4天观察到的水平相似的低水平。注射E2并未改变Muc-1的表达，表明Muc-1的下调是以P为主导的事件。这在卵巢切除的未孕小鼠中得到证实，这些小鼠在注射E2 6小时后Muc-1表达受到刺激。E2刺激的Muc-1表达被纯抗雌激素ICI 164,384抑制。虽然单独的P对Muc-1表达没有影响，但它拮抗E2的作用。在妊娠第3天给妊娠小鼠注射抗孕激素RU486（一种已知的着床抑制剂），可使第4天Muc-1 mRNA恢复高水平表达，表明Muc-1的下调是由P受体介导的。总体而言，这些数据表明小鼠子宫上皮中的Muc-1表达受卵巢类固醇的强烈影响。有人提出，Muc-1的缺失有助于形成子宫接受态。
