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-Ala(6))-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.