PRODUCTION OF MATRIX METALLOPROTEINASE-1 (INTERSTITIAL COLLAGENASE) AND MATRIX METALLOPROTEINASE-2 (GELATINASE-A, 72-KDA GELATINASE) BY OVINE ENDOMETRIAL CELLS IN-VITRO - DIFFERENT REGULATION AND PREFERENTIAL EXPRESSION BY STROMAL FIBROBLASTS
La. Salamonsen et al., PRODUCTION OF MATRIX METALLOPROTEINASE-1 (INTERSTITIAL COLLAGENASE) AND MATRIX METALLOPROTEINASE-2 (GELATINASE-A, 72-KDA GELATINASE) BY OVINE ENDOMETRIAL CELLS IN-VITRO - DIFFERENT REGULATION AND PREFERENTIAL EXPRESSION BY STROMAL FIBROBLASTS, Journal of Reproduction and Fertility, 98(2), 1993, pp. 583-589
Ovine endometrial cells (epithelial plus stromal), prepared from ovari
ectomized ewes treated with oestrogen and progesterone to mimic the lu
teal phase of the oestrous cycle were maintained in serum-free medium
for 48 h in the presence or absence of phorbol myristate acetate (PMA,
100 nmol l-1), a known stimulus for production of matrix metalloprote
inases (MMP) in other cells. Matrix metalloproteinase-1 (MMP-1, inters
titial collagenase) and matrix metalloproteinase-2 (MMP-2, gelatinase
A) activities were expressed by the cells in the absence of PMA; most
were in the latent form and required activation by (4-aminophenyl) mer
curic acetate (APMA). Exposure to PMA over 48 h resulted in a signific
ant increase in MMP-1 activity but only a modest and nonsignificant in
crease in MMP-2 activity. Gelatin zymography demonstrated that proMMP-
2 (72 kDa) was produced by both PMA-treated and untreated cells and an
active form of 67 kDa was also present. Immunolocalization of MMP-1 a
nd MMP-2 was seen within the cells following treatment with monensin.
Highly purified epithelial and stromal cells were similarly cultured a
nd analysis of the conditioned medium showed that MMP-1 and MMP-2 were
produced predominantly by stromal rather than epithelial cells. Thus,
both MMP-1, which degrades interstitial collagens, and MMP-2, an impo
rtant enzyme for degradation of type IV and V collagens, are synthesiz
ed and released by ovine endometrial stromal cells in culture, but MMP
-1 is produced primarily upon stimulation, whereas MMP-2 production is
constitutive. It is postulated that these enzymes have important role
s in endometrial remodelling and implantation.