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.
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.


METHODS
Continuation of prospective randomized study using surgical models for adhesion formation.


METHODS
Department of Obstetrics and Gynecology research laboratory at the University of Missouri School of Medicine.


METHODS
Forty reproductively cycling female Sprague-Dawley rats.


METHODS
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.


METHODS
Peritoneal fluid was analyzed for PA, PAI, MMP, and MMPI activities.


RESULTS
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.


CONCLUSIONS
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.
Sharpe-Timms
K L
KL
University of Missouri, Columbia 65212, USA.
Zimmer
R L
RL
Jolliff
W J
WJ
Wright
J A
JA
Nothnick
W B
WB
Curry
T E
TE
D000818:Animals; D004195:Disease Models, Animal; D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D016729:Leuprolide / Q000627:therapeutic use*; D008666:Metalloendopeptidases / Q000032:analysis* / Q000037:antagonists & inhibitors; D010960:Plasminogen Activators / Q000032:analysis*; D015849:Plasminogen Inactivators / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000517:prevention & control*
D015849:Plasminogen Inactivators; D010960:Plasminogen Activators; D008666:Metalloendopeptidases; D016729:Leuprolide