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Autocrine role of gonadotropin-releasing hormone and its receptor in ovarian cancer cell growth

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Abstract

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 d2 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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of British Columbia, 2H-30, 4490 Oak Street, V6H 3V5, Vancouver, British Columbia, Canada

    Sung K. Kang, Kwai W. Cheng, Parimal S. Nathwani, Kyung-Chul Choi &  Peter C. K. Leung

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  1. Sung K. Kang
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  2. Kwai W. Cheng
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  3. Parimal S. Nathwani
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  4. Kyung-Chul Choi
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  5. Peter C. K. Leung
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Correspondence to Peter C. K. Leung.

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Kang, S.K., Cheng, K.W., Nathwani, P.S. et al. Autocrine role of gonadotropin-releasing hormone and its receptor in ovarian cancer cell growth. Endocr 13, 297–304 (2000). https://doi.org/10.1385/ENDO:13:3:297

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