Lockwood C J, Krikun G, Papp C, Aigner S, Nemerson Y, Schatz F
Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine, New York, New York 10029.
J Clin Endocrinol Metab. 1994 Sep;79(3):786-90. doi: 10.1210/jcem.79.3.8077362.
Despite the pronounced hemorrhagic effects of RU 486 administration on luteal phase and early gestational endometrium, no information is available on the effect of RU 486 on endometrial hemostatic potential. The expression of endometrial stromal cell tissue factor (TF), the primary initiator of hemostasis, has been shown to be progestationally regulated in vivo and in vitro. To evaluate the effects of RU 486 on progestin-enhanced TF expression, confluent stromal cell cultures derived from proliferative phase endometria were exposed to vehicle control, 10(-8) mol/L estradiol (E2), 10(-6) mol/L dexamethasone, 10(-7) mol/L medroxyprogesterone acetate (MPA), E2 plus MPA, E2 plus 10(-6) mol/L progesterone (P), or 10(-6) mol/L RU 486 alone or with E2 plus MPA or E2 plus P for 3-4 days. Compared to the vehicle control, E2, dexamethasone, and RU 486 alone had no effect on the content of immunoreactive and functionally active TF protein, whereas MPA increased and the combination of E2 and MPA further increased TF protein content. Similarly, E2 and P enhanced the stromal cell TF content. These progestin effects were blocked by RU 486. Similar results were obtained for steady state TF messenger ribonucleic acid (mRNA) levels. Possible RU 486-mediated reversal of progestin-enhanced stromal cell TF expression was assessed by incubating confluent cultures in E2 plus MPA for 3-10 days to enhance TF content, then washing the cultures and reexposing them to either E2 plus MPA or to RU 486 alone or with E2 plus MPA for 3, 4, or 7 days. Exposure to RU 486 alone or with E2 plus MPA greatly reduced levels of stromal cell TF protein and mRNA expression compared to those in cultures maintained in E2 plus MPA. These findings demonstrate that RU 486 not only blocks but also reverses in vitro progestin-enhanced stromal cell TF protein and mRNA expression, suggesting an additional mechanism for RU 486-induced menses and early abortion.
尽管米非司酮对黄体期和孕早期子宫内膜有明显的出血作用，但关于米非司酮对子宫内膜止血潜能的影响尚无相关信息。子宫内膜基质细胞组织因子（TF）是止血的主要启动因子，其表达在体内和体外均受孕激素调节。为评估米非司酮对孕激素增强的TF表达的影响，将来自增殖期子宫内膜的汇合基质细胞培养物分别暴露于溶媒对照、10⁻⁸ mol/L雌二醇（E2）、10⁻⁶ mol/L地塞米松、10⁻⁷ mol/L醋酸甲羟孕酮（MPA）、E2加MPA、E2加10⁻⁶ mol/L孕酮（P），或单独使用10⁻⁶ mol/L米非司酮，或与E2加MPA或E2加P联合处理3 - 4天。与溶媒对照相比，单独使用E2、地塞米松和米非司酮对免疫反应性和功能活性TF蛋白含量无影响，而MPA可增加TF蛋白含量，E2与MPA联合使用则进一步增加TF蛋白含量。同样，E2和P可增强基质细胞TF含量。这些孕激素作用被米非司酮阻断。稳态TF信使核糖核酸（mRNA）水平也得到了类似结果。通过将汇合培养物在E2加MPA中孵育3 - 10天以增加TF含量，然后洗涤培养物并将其重新暴露于E2加MPA或单独的米非司酮或与E2加MPA联合处理3、4或7天，评估米非司酮介导的孕激素增强的基质细胞TF表达逆转的可能性。与维持在E2加MPA中的培养物相比，单独暴露于米非司酮或与E2加MPA联合处理可显著降低基质细胞TF蛋白水平和mRNA表达。这些发现表明，米非司酮不仅能阻断，还能逆转体外孕激素增强的基质细胞TF蛋白和mRNA表达，提示米非司酮诱导月经和早期流产的另一种机制。
