Promotion of human trophoblasts invasion by gonadotropin-releasing hormone (GnRH) I and GnRH II via distinct signaling pathways.
The potential roles of GnRH I and GnRH II have been assigned in promoting the invasive capacity of human trophoblasts by regulating matrix metalloproteinases-2 and -9, type I tissue inhibitor of matrix metalloproteinase, and urokinase plasminogen activator/plasminogen activator inhibitor protease systems during human placentation, and GnRH II has been shown to be more potent than GnRH I. However, the mechanisms for the differential effects of these two hormones remain unclear. In this study, we examined the invasion-promoting effects and the signaling pathways of GnRH I and GnRH II in human trophoblasts. The data revealed that both GnRH I and GnRH II were key autocrine and/or paracrine regulators in facilitating trophoblast invasion. The GnRH receptor antagonist (Antide) and specific small interfering RNA for GnRH receptor inhibited the regulatory effects of GnRH I, but not GnRH II, on trophoblast invasion. Both GnRH I and II activated protein kinase C, ERK1/2, and c-Jun N-terminal kinase to mediate their effects on trophoblast invasion, whereas only GnRH II elicited invasion-promoting action through transactivating the tyrosine kinase activity of epidermal growth factor receptor in trophoblasts. Our observations elucidate a ligand-dependent selective cross-communication between GnRH receptor and epidermal growth factor receptor signaling systems in human trophoblastic cell, and this would further our understanding on the differentially biological significance of these two forms of GnRH in extrapituitary tissues.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
Jing
J
Liu
Colin D
CD
Maccalman
Yan-ling
YL
Wang
Peter C K
PC
Leung
D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014327:Trophoblasts / Q000187:drug effects* / Q000502:physiology
D009842:Oligopeptides; D011498:Protein Precursors; D034741:RNA, Small Interfering; D011966:Receptors, LHRH; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone; C047717:LHRH, His(5)-Trp(7)-Tyr(8)-; C057022:iturelix; C512478:EGFR protein, human; D066246:ErbB Receptors; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9