The effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human extravillous cytotrophoblasts in vitro.
The regulated expression of the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) is believed to modulate the invasive capacity of human trophoblastic cells in vitro and in vivo. To date, the factors capable of regulating the expression of uPA and PAI-1 in these cells remain poorly characterized. In these studies, we have examined the ability of the classical mammalian GnRH I and the second form of GnRH (GnRH II) to regulate uPA and PAI-1 mRNA and protein expression levels in primary cultures of human extravillous cytotrophoblasts using quantitative competitive PCR and ELISA, respectively. Both GnRH I and II increased uPA and concomitantly decreased PAI-1 mRNA and protein expression levels in our extravillous cytotrophoblast cultures in a dose- and time-dependent manner. Cetrorelix, a peptide GnRH antagonist specific for the GnRH I receptor, was capable of inhibiting the regulatory effects of GnRH I, but not GnRH II on uPA and PAI-1 expression levels in primary cell cultures. Taken together, these observations suggest that GnRH I and GnRH II may facilitate trophoblast invasion by increasing the ratio of uPA/PAI-1 expression via interactions with two distinct GnRH receptors.
Chou
Chun-Shan
CS
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5.
Zhu
Hua
H
Shalev
Eliezer
E
MacCalman
Colin D
CD
Leung
Peter C K
PC
D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D006727:Hormone Antagonists; D017395:Plasminogen Activator Inhibitor 1; D020033:Protein Isoforms; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D014568:Urokinase-Type Plasminogen Activator; C062876:cetrorelix