Regulation of matrix metalloproteinases and their inhibitors in uterine endometrial cells of patients with and without endometriosis

Eur J Obstet Gynecol Reprod Biol. 2001 Apr;95(2):167-74. doi: 10.1016/s0301-2115(00)00415-2.


Objective: To determine whether alterations in the secretion and regulation of matrix metalloproteinases (MMPs) and their inhibitors are present in uterine endometrial cells from endometriosis patients.

Study design: In an in vitro study, uterine endometrial cells from 19 regularly cycling women with and 32 without endometriosis were treated with diethyl stilbestrol, promegestone (R5020), interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha). Culture supernatants were assayed for MMPs 1, 2, 3, and 9, and for tissue inhibitors of MMP (TIMP-1 and TIMP-2) by ELISA.

Results: MMP-3 was secreted in high concentrations, moderate concentrations were seen for MMP-1 and MMP-2, and very low concentrations for MMP-9. Substantially more TIMP-1 than TIMP-2 was secreted. MMP-1 and MMP-3 were uniformly attenuated by R5020, while MMP-2 was not influenced by hormone treatment. MMP-3 was upregulated by TNF-alpha in all samples while IL-1 only increased secretion in cells from endometriosis patients.

Conclusion: The upregulation of MMP-3 by IL-1 may contribute to an increased invasiveness of uterine endometrial fragments in endometriosis patients.

MeSH terms

  • Adult
  • Cells, Cultured
  • Diethylstilbestrol / pharmacology
  • Endometriosis / enzymology*
  • Endometrium / enzymology*
  • Female
  • Humans
  • Interleukin-1 / pharmacology
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Promegestone / pharmacology
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tissue Inhibitor of Metalloproteinases / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Interleukin-1
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinases
  • Tumor Necrosis Factor-alpha
  • Tissue Inhibitor of Metalloproteinase-2
  • Diethylstilbestrol
  • Promegestone
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1