Abstract
Objective: To evaluate the effects of a gonadotropin-releasing hormone agonist (GnRH-a) on plasminogen activator (PA), matrix metalloproteinase (MMP), plasminogen activator inhibitor (PAI) and matrix metalloproteinase inhibitor (MMPI) activities in peritoneal fluid relative to GnRH-a-induced reduction of adhesion formation. Design: Continuation of prospective randomized study using surgical models for adhesion formation. Setting: Department of Obstetrics and Gynecology research laboratory at the University of Missouri School of Medicine. Patient(s): Forty reproductively cycling female Sprague-Dawley rats. Intervention(s): Female rats were injected with depot GnRH-a or diluent and randomly assigned to adhesion and endometriosis surgeries. Peritoneal fluid was collected prior to (time 1) and 7 weeks from (time 2) initial surgery. Main Outcome Measure(s): Peritoneal fluid was analyzed for PA, PAI, MMP, and MMPI activities. Result(s): At time 1, MMP and MMPI activities were similar in all rats; however, PA and PAI activities were less in rats pretreated with GnRH-a than with diluent. Between time 1 and time 2, GnRH-a-treated rats showed an increase in PAI and MMPI activities without significant changes in PA or MMP activities, whereas rats receiving diluent showed a significant increase in PAl and MMP activities but no significant changes in PA or MMPI activities. At time 2, rats receiving GnRH- a had less PA and MMP activities than those receiving diluent. Adhesion scores showed a positive correlation with MMP activity. Conclusion(s): In the absence of GnRH-a therapy, surgical tissue manipulation increased peritoneal fluid MMP and PAI activity. Gonadotropin-releasing hormone agonist therapy decreased PA and MMP activities and also increased PAI and MMPI activities. This GnRH-a-induced shift to a less invasive phenotype may alter fibrinolysis and extracellular matrix remodeling and thereby play a role in the mechanism of GnRH-a-induced reduction in adhesion formation.
Original language | English |
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Pages (from-to) | 916-923 |
Number of pages | 8 |
Journal | Fertility and Sterility |
Volume | 69 |
Issue number | 5 |
DOIs | |
State | Published - May 1998 |
Bibliographical note
Funding Information:Supported in part by grants HD29026 (K.L.S.-T.) and HD 273995 (T.E.C.) from the National Institutes of Health, Bethesda, Maryland. Additional support provided by TAP Pharmaceuticals, Inc., Deerfield, Illinois.
Keywords
- Adhesions
- Endometriosis
- Enzyme inhibitors
- Matrix metalloproteinase
- Peritoneum
- Plasminogen activator
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology