Human endometrial matrix metalloproteinase-2, a putative menstrual proteinase - Hormonal regulation in cultured stromal cells and messenger RNA expression during the menstrual cycle
Human endometrial matrix metalloproteinase-2, a putative menstrual proteinase - Hormonal regulation in cultured stromal cells and messenger RNA expression during the menstrual cycle
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人子宫内膜基质金属蛋白酶-2（一种假定的月经蛋白酶）--月经周期中激素对培养基质细胞的调控和信使 RNA 的表达
DOI：
10.1172/jci118433
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发表时间：
1996-01-15
影响因子：
15.9
通讯作者：
Giudice, LC
中科院分区：
文献类型：
--
作者：
Irwin, JC;Kirk, D;Giudice, LC
蛋白酶可能是子宫内膜月经破裂的影响因素。我们研究了人子宫内膜间质细胞在孕酮（P）撤除（月经的生理刺激）后蛋白酶的产生。暴露于雌二醇，P，或雌二醇加P的细胞培养基具有低水平的蛋白水解活性，类似于在不存在类固醇的情况下维持的培养物。P撤出，或添加RU 486到P处理的培养物，刺激蛋白酶分泌。基质细胞蛋白酶的特点是明胶酶谱，抑制剂配置文件，和有机汞活化，作为金属蛋白酶目前主要作为一个66 kD的酶原与较低水平的62 kD的活性形式。停磷诱导的基质金属蛋白酶经Western blotting鉴定为基质金属蛋白酶-2（MMP-2）。停磷诱导的MMP-2的增加与基质金属蛋白酶依赖性的基质细胞降解有关，包括细胞外基质的溶解和基质细胞的解离。北方分析显示，分泌晚期子宫内膜中MIMP-2 mRNA的表达存在差异。这些发现与基质细胞衍生的MMP-2参与细胞外基质的蛋白水解促进周期性子宫内膜破裂和月经出血的发生是一致的。
Proteinases are likely effecters of endometrial menstrual breakdown. We have investigated proteinase production by human endometrial stromal cells subjected in vitro to progesterone (P) withdrawal, the physiologic stimulus for menstruation. Culture media of cells exposed to estradiol, P, or estradiol plus P had low levels of proteolytic activity similar to cultures maintained in the absence of steroids. P withdrawal, or addition of RU486 to P-treated cultures, stimulated proteinase secretion. The stromal cell proteinase was characterized by gelatin zymography, inhibitor profile, and organomercurial activation, as a metalloproteinase present mostly as a 66-kD proenzyme with lower levels of a 62-kD active form. The P withdrawal-induced metalloproteinase was identified as matrix metalloproteinase-2 (MMP-2) by Western blotting, The increase of MMP-2 induced by P withdrawal was associated with the metalloproteinase-dependent breakdown of stromal cultures, involving dissolution of extracellular matrix and dissociation of stromal cells. Northern analysis showed the differential expression of MIMP-2 mRNA in late secretory phase endometrium. These findings are consistent with the involvement of stromal cell-derived MMP-2 in the proteolysis of extracellular matrix promoting cyclic endometrial breakdown and the onset of menstrual bleeding.