Objective: To investigate the regulation of perimenstrual MMP-1 expression in human endometrium. Design: In vitro study utilizig epithelial-stromal co-cultures. Setting: Cell Biology Unit, International Institute of Cellular and Molecular Pathology, and De- partments of Pathology and Gynecology, Saint-Luc University Clinics, Louvain University Medi- cal School, Brussels, Belgium. Methods: Contact-dependent and contact-independent co-cultures were established and resulting MMP-1 gene and protein expression was analyzed by RNase protection assays and soluble-colla- gen assays. Results: MMP-1 expression in endometrial fibroblasts is markedly stimulated by epithelial cell- conditioned medium. This stimulation can be prevented by antibodies directed against interleu- kin 1alpha (IL-1alpha). Ovarian steroids inhibit MMP-1 production by IL-1alpha-stimulated fibroblasts in vitro. Conclusion: Taken together, our results suggest that epithelium-derived IL-1alpha is the most important paracrine induced of MMP-1 in endometrial fibroblasts. However, IL-1a-stimulated MMP-1 production in the human endometrium is effectively blocked by ovarian steroids. We believe that this mechanism responsible for the MMP-1 repression that occurs when systemic sex steroid concentrations are high and the MMP-1 production and activity during the perimenstrual phase when estrogen and progesterone concentrations are low.

        Key words: MMP-1, human endometrium, sex steroids, menstruation