Kang S K, Cheng K W, Nathwani P S, Choi K C, Leung P C
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
Endocrine. 2000 Dec;13(3):297-304. doi: 10.1385/ENDO:13:3:297.
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.
我们最近提出促性腺激素释放激素（GnRH）及其受体（GnRH-R）在人卵巢表面上皮细胞中具有自分泌作用。在本研究中，我们检测了GnRH/GnRH-R环路在卵巢癌细胞OVCAR-3中的存在及作用。用GnRH激动剂[GnRHa，（D-Ala6）-GnRH]处理24小时后，观察到GnRH和GnRH-R mRNA水平呈剂量依赖性双相反应。高浓度的GnRHa（10^(-9) M和10^(-7)）降低了GnRH和GnRH-R mRNA水平，而低浓度（10^(-11) M）则导致GnRH和GnRH-R基因表达上调。与竞争性拮抗剂antide共同处理可阻止GnRHa诱导的双相效应，证实了反应的特异性。此外，GnRHa处理对OVCAR-3细胞生长产生时间和剂量依赖性抑制。早在处理第2天就检测到增殖受到显著抑制。用10^(-7) M GnRHa处理诱导OVCAR-3细胞DNA片段化，表明GnRHa诱导的OVCAR-3细胞抗增殖作用是由凋亡介导的。同样，antide共同处理可阻止这种效应。综上所述，我们的研究结果有力地支持了GnRH作为卵巢癌细胞增殖的自分泌/旁分泌调节因子的观点。
