title: Metalloproteinases and tissue inhibitor of metalloproteinase 1 (TIMP-1) in endometrial flushings from pre- and post-menopausal women and from women with endometrial adenocarcinoma.
abstract: The presence of metalloproteinase activity in endometrial flushings obtained from premenopausal women, during the proliferative and secretory phases of the menstrual cycle, control post-menopausal women and women with post-menopausal bleeding (PMB) with or without adenocarcinoma was analysed by zymography. In addition, quantitative measurements of matrix metalloproteinase 2 (MMP-2), MMP-3, MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) in the flushings were obtained by ELISA. The zymography results showed eight bands of activity, with molecular weights ranging from 51 to 208 kDa in the flushings from pre-menopausal women and post-menopausal women, particularly those with adenocarcinoma. Both zymography and ELISA showed that MMP-2 and MMP-9 were the major metalloproteinases found in the flushings and only low concentrations of MMP-3 were found. Concentrations of MMP-2 in pre-menopausal women were higher in flushings obtained during the secretory phase of the menstrual cycle than those obtained in the proliferative phase (P < 0.05), suggesting that it may play a role in embryo implantation. Concentrations of MMP-2 (P < 0.001), MMP-9 (P < 0.05) and TIMP-1 (P < 0.001) in the flushings from post-menopausal control women were lower than those from pre-menopausal women. Concentrations of MMP-2 (P < 0.05) and TIMP-1 (P < 0.05) were higher in flushings from women with PMB without carcinoma compared with post-menopausal controls and concentrations of MMP-9 (P < 0.01) and TIMP-1 (P < 0.05) in flushings from women with adenocarcinoma were higher than in post-menopausal controls. Among subjects with PMB, concentrations of MMP-9 in women with adenocarcinoma were higher than those without carcinoma (P < 0.05). Our results show that concentrations of MMP-2, MMP-9 and TIMP-1, but not MMP-3, are associated with endometrial activity and, therefore, may have a role in the breakdown of endometrial tissue. In addition, the increased concentrations of MMP-9 in flushings of women with adenocarcinoma indicate that this particular proteinase is associated with the presence of endometrial neoplastic cells.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Laird
authors.forename: C F
authors.initials: CF
authors.lastname: Dalton
authors.forename: M A
authors.initials: MA
authors.lastname: Okon
authors.forename: R A
authors.initials: RA
authors.lastname: Bunning
authors.forename: R
authors.initials: R
authors.lastname: Marshall
authors.forename: T C
authors.initials: TC
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017364:Collagenases / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D016889:Endometrial Neoplasms / Q000201:enzymology*; D004717:Endometrium / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005498:Follicular Phase / Q000378:metabolism; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D008183:Luteal Phase / Q000378:metabolism; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9; D008593:Menopause / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9