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, Sharpe-Timms KL, K L Sharpe-Timms, Zimmer RL, Randall L. Zimmer, R L Zimmer, Wendy J. Jolliff, Jolliff WJ, W J Jolliff, Wright JA, Jean Ann Wright, J A Wright, Warren B. Nothnick, Nothnick WB, W B Nothnick, Thomas E. Curry, T E Curry, Curry TE
Fertility and Sterility · 1998 · vol. 69(5) , pp. 916–923 · doi:10.1016/s0015-0282(98)00032-6 · PMID:9591503 · W1837228878
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Gonadotropin-releasing hormone agonist therapy in rats reduced adhesion formation by decreasing peritoneal fluid plasminogen activator and matrix metalloproteinase activities while increasing inhibitor activities.

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Abstract

ObjectiveTo 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.DesignContinuation of prospective randomized study using surgical models for adhesion formation.SettingDepartment 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 PAI 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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Leuprolide Metalloendopeptidases Plasminogen Activators Plasminogen Inactivators Tissue Adhesions Animals Disease Models, Animal Endometriosis Female Leuprolide Metalloendopeptidases Metalloendopeptidases Plasminogen Activators Plasminogen Inactivators Rats Rats, Sprague-Dawley Tissue Adhesions

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