Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floor

Objective: The purpose of this study was to determine whether estrogen suppresses matrix metalloproteinase-2 and -9 proenzyme expression by fibroblasts that are derived from the supportive connective tissue of the pelvic floor. Study Design: A primary fibroblast culture that was developed from a biopsy specimen of the arcus tendineus was treated with interleukin-1β (10-15 ng/mL), transforming growth factor-β1 (5-15 ng/mL), 17β-estradiol (10−9−10−7 mol/L), and Imperial Chemical Industries (ICI) 182 780 (10−8−10−6 mol/L). Cellular and extracellular protein were analyzed by Western blotting and substrate zymography, respectively, for the effect of each treatment on the amount of pro-matrix metalloproteinase-2 and -9 and the membrane type 1 matrix metalloproteinase protein. Results: Both cellular and extracellular pro-matrix metalloproteinase-2 protein were increased by transforming growth factor-β1 (P = .01) and decreased by estradiol (P < .001) and ICI 182 780 (P = .02 and .002, respectively). Membrane type 1 matrix metalloproteinase was not affected by estradiol, ICI 182 780, interleukin-1β, or transforming growth factor-β1. Extracellular pro-matrix metalloproteinase-9 was increased by the cytokines interleukin-1β (P < .001) and transforming growth factor-β1 (P < .001) and decreased by estradiol (P < .001) and ICI 182 780 (P < .001). Conclusion: The proenzymes of the tissue-degrading matrix metalloproteinases -2 and -9 are decreased by 17-β estradiol and ICI 182 780 . (Am J Obstet Gynecol 2002;187:72-9.)