FOCAL CELLULAR-ORIGIN AND REGULATION ON INTERSTITIAL COLLAGENASE (MATRIX METALLOPROTEINASE-1) ARE RELATED TO MENSTRUAL BREAKDOWN IN THE HUMAN ENDOMETRIUM

Recent studies suggest that interstitial collagenase (MMP-1) is an ess ential enzyme in the early events leading to menstruation, This study analyses its cellular origin, regulation and relation to extracellular matrix breakdown in the human endometrium, both in cultured and non-c ultured samples, The source of MMP-1 was identified by in situ hybridi zation and by immunohistochemistry on serial sections, This was compar ed with the immunolocalization of other MMPs, steroid receptors, macro phages, and laminin, In non-cultured endometrium, MMP-1 was only expre ssed during the perimenstrual period, It was either restricted to supe rficial foci of stromal cells or extended towards the entire functiona l layer, MMP-1 expression remarkably correlated with matrix breakdown, as assessed by silver staining, and was prominent at the periphery of shedding fragments and along some arterioles, In cultured non-menstru al explants, MMP-1 expression was induced within two days after depriv ation of sex steroids, Both in cultured and non-cultured samples, prog esterone receptors were not detectable in epithelial cells at foci of MMP-1 expression, The same stromal cells could synthesize MMP-1, MMP-2 (gelatinase A) and MMP-3 (stromelysin-1), as well as laminin, and did not correspond to macrophages. In conclusion, MMP-1 is focally expres sed in stromal cells of the functional layer of the endometrium, when and where steroid receptors disappear, and especially where tissue bre akdown is prominent, These observations point to an essential role for MMP-1 in the early stages of menstruation.