Human endometrial matrix metalloproteinase-2, a putative menstrual proteinase - Hormonal regulation in cultured stromal cells and messenger RNA expression during the menstrual cycle

被引:97
作者
Irwin, JC
Kirk, D
Gwatkin, RBL
Navre, M
Cannon, P
Giudice, LC
机构
[1] STANFORD UNIV,MED CTR,DEPT OBSTET & GYNECOL,STANFORD,CA 94305
[2] HUNTINGTON MED RES INST,PASADENA,CA 91101
[3] CASE WESTERN RESERVE UNIV,SCH MED,DEPT REPROD BIOL,CLEVELAND,OH 44106
[4] REPROGENE,CLEVELAND,OH 44106
[5] SYNTEX INC,RES,PALO ALTO,CA 94303
关键词
endometrium; menstruation; uterine bleeding; gelatinase A; type IV collagenase;
D O I
10.1172/JCI118433
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:438 / 447
页数:10
相关论文
共 57 条
[51]  
WAGNER H, 1979, BIOL FLUIDS FEMALE G, P187
[52]  
WERB Z, 1985, TXB RHEUMATOLOGY, P300
[53]  
WEWER UM, 1985, LAB INVEST, V53, P624
[54]   MATRIX METALLOPROTEINASES AND THEIR INHIBITORS IN CONNECTIVE-TISSUE REMODELING [J].
WOESSNER, JF .
FASEB JOURNAL, 1991, 5 (08) :2145-2154
[55]  
WOESSNER JF, 1988, J BIOL CHEM, V263, P16918
[57]  
WOOD J C, 1969, Journal of Obstetrics and Gynaecology of the British Commonwealth, V76, P724