Differential effects of gonadotropin-releasing hormone I and II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human decidual stromal cells in vitro.
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.
Chou
Chun-Shan
CS
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5.
MacCalman
Colin D
CD
Leung
Peter C K
PC
D000328:Adult; D002469:Cell Separation; D002478:Cells, Cultured; D017931:DNA Primers; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015849:Plasminogen Inactivators / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology*
D017931:DNA Primers; D006727:Hormone Antagonists; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D014568:Urokinase-Type Plasminogen Activator; C062876:cetrorelix