Autocrine role of gonadotropin-releasing hormone and its receptor in ovarian cancer cell growth.
We have recently proposed an autocrine role of gonadotropin-releasing hormone (GnRH) and its receptor (GnRH-R) in human ovarian surface epithelium. In the present study, we examine the presence and role of a GnRH/GnRH-R loop in epithelial ovarian cancer cells, OVCAR-3. A dose-dependent biphasic response in GnRH and GnRH-R mRNA levels were observed after treating with GnRH agonist [GnRHa, (D-Ala6)-GnRH], for 24 h. High concentrations of GnRHa (10(-9) M and 10(-7)) decreased the GnRH and GnRH-R mRNA levels, whereas a low concentration (10(-11) M) resulted in an upregulation of GnRH and GnRH-R genes expression. Cotretment with the competitive antagonist, antide, prevented the biphasic effect induced by GnRHa, confirming the specificity of the response. In addition, GnRHa treatment resulted in a time- and dose-dependent inhibition on OVCAR-3 cells growth. A significant inhibition of proliferation was detected as early as the d 2 of treatment. Treatment with 10(-7) M GnRHa induced DNA fragmentation in OVCAR-3 cells, suggesting that the GnRHa-induced antiproliferation in OVCAR-3 cells was mediated by apoptosis. Again, this effect was prevented by cotreatment of antide. Taken together, our findings strongly support the notion that GnRH acts as an autocrine/paracrine regulator of ovarian cancer cell proliferation.
Kang
S K
SK
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
Cheng
K W
KW
Nathwani
P S
PS
Choi
K C
KC
Leung
P C
PC
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011966:Receptors, LHRH / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix