Gonadotropin-releasing hormone agonist (GnRH-a) therapy alters activity of plasminogen activators, matrix metalloproteinases, and their inhibitors in rat models for adhesion formation and endometriosis: Potential GnRH-a- regulated mechanisms reducing adhesion formation

Kathy L. Sharpe-Timms, Randall L. Zimmer, Wendy J. Jolliff, Jean A. Wright, Warren B. Nothnick, Thomas E. Curry

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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 languageEnglish
Pages (from-to)916-923
Number of pages8
JournalFertility and Sterility
Volume69
Issue number5
DOIs
StatePublished - 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

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