Schatz F, Lockwood C J
Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, New York, New York 10029.
J Clin Endocrinol Metab. 1993 Sep;77(3):621-5. doi: 10.1210/jcem.77.3.8370684.
The progestin medroxyprogesterone acetate (MPA) enhanced expression of the endothelial-type plasminogen activator inhibitor PAI-1 by stromal cells from cycling endometrium and by decidual cells from first trimester endometrium. In the cultured stromal cells, Northern analysis revealed a 4-fold increase in steady state levels of PAI-1 mRNA in response to 10(-6)-10(-8) mol/L MPA. Although the cells were refractory to 10(-8) mol/L estradiol (E2) alone, E2 plus MPA produced a further doubling of PAI-1 mRNA levels. Parallel effects on PAI-1 protein levels in the stromal cell-conditioned medium were measured by immunoassay and confirmed by immunoblot analysis. During an initial 3-day exposure, PAI-1 levels were elevated 6- and 12-fold by MPA and E2 plus MPA, respectively, compared with those in either control or E2-treated cells. In the subsequent 3 days of culture, PAI-1 levels were increased 30-fold by MPA and 70-fold by E2 plus MPA. Cultured decidual cells released significant quantities of PAI-1 under basal conditions; these levels were also elevated by MPA and increased markedly by E2 plus MPA. While PAI-2 was also detected in both stromal and decidual cell cultures, its levels were far lower than those of PAI-1 and were unaffected by exogenous steroids. Extrapolation of these in vitro results to periimplantational events in humans suggests that under progesterone regulation, decidual cell-derived PAI-1 could 1) restrain blastocyst invasion of the stroma by inhibiting trophoblast-associated urokinase-type plasminogen activator, and 2) prevent hemorrhage during trophoblast invasion of the endometrial vasculature by inhibiting fibrinolysis mediated by tissue-type plasminogen activator.
孕激素醋酸甲羟孕酮（MPA）可增强来自周期性子宫内膜的基质细胞以及来自孕早期子宫内膜的蜕膜细胞中内皮型纤溶酶原激活物抑制剂PAI-1的表达。在培养的基质细胞中，Northern分析显示，在10⁻⁶ - 10⁻⁸ mol/L MPA作用下，PAI-1 mRNA的稳态水平增加了4倍。尽管这些细胞单独对10⁻⁸ mol/L雌二醇（E2）不敏感，但E2加MPA使PAI-1 mRNA水平进一步加倍。通过免疫测定法测量了对基质细胞条件培养基中PAI-1蛋白水平的平行影响，并通过免疫印迹分析得到证实。在最初3天的暴露期间，与对照或E2处理的细胞相比，MPA和E2加MPA分别使PAI-1水平升高了6倍和12倍。在随后3天的培养中，MPA使PAI-1水平增加了30倍，E2加MPA使PAI-1水平增加了70倍。培养的蜕膜细胞在基础条件下释放大量PAI-1；这些水平也因MPA而升高，并因E2加MPA而显著增加。虽然在基质细胞和蜕膜细胞培养物中也检测到了PAI-2，但其水平远低于PAI-1，并且不受外源性类固醇的影响。将这些体外结果外推至人类着床前后的事件表明，在孕酮调节下，蜕膜细胞衍生的PAI-1可能：1）通过抑制滋养层相关的尿激酶型纤溶酶原激活物来抑制胚泡对基质的侵袭，以及2）通过抑制组织型纤溶酶原激活物介导的纤维蛋白溶解来防止滋养层侵袭子宫内膜血管系统期间的出血。
