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.


METHODS
A primary fibroblast culture that was developed from a biopsy specimen of the arcus tendineus was treated with interleukin-1 beta (10-15 ng/mL), transforming growth factor-beta 1 (5-15 ng/mL), 17 beta-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-beta1 (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-1 beta, or transforming growth factor-beta 1. Extracellular pro-matrix metalloproteinase-9 was increased by the cytokines interleukin-1 beta (P <.001) and transforming growth factor-beta1 (P <.001) and decreased by estradiol (P <.001) and ICI 182 780 (P <.001).


CONCLUSIONS
The proenzymes of the tissue-degrading matrix metalloproteinases -2 and -9 are decreased by 17-beta estradiol and ICI 182 780.
Department of Obstetrics and Gynecology and Division of Gynecologic Specialties, Magee-Womens Hospital and Magee-Womens Research Institute, University of Pittsburgh, PA 15213, USA.
Pamela A
PA
Moalli
Wendy L
WL
Klingensmith
Leslie A
LA
Meyn
Halina M
HM
Zyczynski
D000328:Adult; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D000077267:Fulvestrant; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D004965:Estrogen Antagonists; D007375:Interleukin-1; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D000077267:Fulvestrant; D004958:Estradiol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9