ASSOCIATION OF PROTEASE ACTIVITY AGAINST IGFBP-3 WITH PERITONEAL-FLUID MITOGENS - POSSIBLE IMPLICATIONS FOR THE ECTOPIC GROWTH OF ENDOMETRIAL CELLS IN WOMEN WITH ENDOMETRIOSIS

Background: Recent data indicate the implication of an IGF/IGFBP/prote ase system in the development of ectopic implants of endometrium (endo metriosis) in the pelvic cavity. Material and methods: We characterize d mitogens and protease(s) against IGFBP-3 in the peritoneal fluid of women with or without endometriosis using preparative isoelectric focu sing (IEC) Proteineous fractions were tested for a) mitogenic activity on NIH/3T3 cells and KLE endometrial-like cells, b) proteinolytic act ivity against radiolabeled IGFBP-3, and c) protein analysis using SDS- PAGE. Results: A significant increase in the DNA content of cultured c ell lines was found in PF fractions having slightly acidic or alkaline pH and containing mainly proteins with molecular weights between 50 a nd 25 kD. These fractions were also found to cleave IGFBP-3 into 25, 1 8 and 14 kD fragments. Both activities were present in the PF of subje cts with or without endometriosis. Conclusion: The preparative isoelec tric focusing system would be an advantageous approach to investigate the possible implication of the PF proteases with IGFBP-3 limited prot eolysis generating PF mitogen(s) which possibly participate in the pat hophysiology of endometriosis.