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Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5
Address all correspondence and requests for reprints to: Peter C. K. Leung, Ph.D., Department of Obstetrics and Gynecology, University of British Columbia, Room 2H-30, 4490 Oak Street, Vancouver, British Columbia, Canada V6H 3V5. E-mail: peleung{at}interchange.ubc.ca.
To date, the factors capable of regulating the coordinate expression of the urokinase-type plasminogen activator (uPA) and its endogenous inhibitor, plasminogen activator inhibitor (PAI-1), at the maternal-fetal interface remain poorly characterized. In these studies we examined the ability of the classical form of gonadotropin-releasing hormone (GnRH) I and the second, mammalian form of this hormone, GnRH II, to regulate uPA and PAI-1 mRNA and protein expression levels in cultures of stromal cells isolated from first trimester decidual tissues using quantitative competitive-PCR and ELISA, respectively. GnRH I and GnRH II increased uPA mRNA and protein expression levels in these primary cell cultures in a dose- and time-dependent manner. In contrast, GnRH I increased, whereas GnRH II decreased PAI-1 mRNA and protein expression levels in these cells. Cetrorelix, a GnRH receptor antagonist, inhibited the regulatory effects of GnRH I, but not GnRH II, on uPA and PAI-1 expression levels in these decidual stromal cell cultures. Taken together, these observations suggest that GnRH I and GnRH II differentially regulate the balance between uPA and PAI-1 expression levels in the human decidua, possibly via distinct receptor-mediated signaling pathways.
This work was supported by an operating grant from the Canadian Institutes of Health Research (to P.C.K.L. and C.D.M.).
C.D.M. and P.C.K.L. contributed equally to these studies.
C.D.M. is a Career Investigator with the British Columbia Research Institute for Childrens and Womens Health.
P.C.K.L. is a Recipient of a Senior Investigatorship from the Michael Smith Foundation for Health Research.
Abbreviations: ECM, Extracellular matrix; EGFR, epidermal growth factor receptor; GnRHR, GnRH receptor; PAI-1, plasminogen activator inhibitor type 1; QC-PCR, quantitative competitive-PCR; uPA, urokinase-type plasminogen activator.
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