Regulatory effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the levels of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 in primary cultures of human extravillous cytotrophoblasts.
An intricate balance between the production of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), modulates the overall proteolytic activity of trophoblasts during human implantation. In these studies we have examined the ability of classical GnRH I and the second form of this hormone (GnRH II) to regulate MMP-2, MMP-9, and TIMP-1 mRNA and protein levels in extravillous cytotrophoblasts propagated from explants of first trimester chorionic villi. GnRH I and GnRH II were found to increase MMP-2 and MMP-9 mRNA and protein levels in these primary cell cultures in a dose- and time-dependent manner using quantitative competitive-PCR and ELISA. In contrast, these two hormones decreased trophoblastic TIMP-1 mRNA and protein levels. Cetrorelix, a GnRH receptor antagonist, inhibited the regulatory effects of GnRH I, but not GnRH II, on MMP-2, MMP-9, and TIMP-1 expression in these cells. Collectively, these observations suggest that GnRH I and GnRH II differentially regulate MMP-2, MMP-9, and TIMP-1 expression in human trophoblasts, possibly via distinct receptor-mediated intracellular signaling pathways.
Chou
Chun-Shan
CS
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5.
Zhu
Hua
H
MacCalman
Colin D
CD
Leung
Peter C K
PC
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*
D006727:Hormone Antagonists; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D007987:Gonadotropin-Releasing Hormone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C062876:cetrorelix