Expression and Antiproliferative Effect of a Second Form of Gonadotropin-Releasing Hormone in Normal and Neoplastic Ovarian Surface Epithelial Cells

Abstract

Epithelial ovarian carcinomas are the most common cause of death from gynecological malignancies and appear to arise from ovarian surface epithelium (OSE), but the exact mechanism of ovarian tumorigenesis has not been elucidated. Recent cloning of a second form of gonadotropin-releasing hormone (GnRH-II) has been reported in various human tissues including the ovary. However, the expression and role of GnRH-II in human OSE and ovarian carcinomas is not known. In the present study, we demonstrated that in addition to the GnRH receptor (GnRH-R), GnRH-II mRNA is expressed in normal OSE, immortalized OSE (IOSE) cells, primary cultures of ovarian tumors and ovarian cancer cell lines. Treatments with increasing doses (10−9–10−7 M) of GnRH-I and -II resulted in a growth-inhibition in both non-tumorigenic IOSE-29 and tumorigenic IOSE-29EC cells. These results indicate for the first time the expression and potential anti-proliferative effect of GnRH-II, suggesting that GnRH-II, similar to GnRH-I, may have a growth-regulatory effect in normal and neoplastic OSE cells.