The Matrix Metalloproteinase-1 (MMP-1)Expression in the Human Endometrium isInversely Regulated by Interleukin-1alpha andSex Steroids*

Overview

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 resultingMMP-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-stimulatedfibroblasts in vitro.Conclusion: Taken together, our results suggest that epithelium-derived IL-1alpha is the mostimportant paracrine induced of MMP-1 in endometrial fibroblasts. However, IL-1a-stimulatedMMP-1 production in the human endometrium is effectively blocked by ovarian steroids. Webelieve that this mechanism responsible for the MMP-1 repression that occurs when systemic sexsteroid concentrations are high and the MMP-1 production and activity during the perimenstrualphase when estrogen and progesterone concentrations are low.

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