Gonadotropin-releasing hormone (GnRH) and GnRH receptor in bladder cancer epithelia and GnRH effect on bladder cancer cell proliferation

Introduction: Gonadotropin-releasing hormone ( GnRH) is the pivotal hormone in the hypothalamopituitary gonadal axis. Recently, localization of extrahypothalamic GnRHs and GnRH receptors has been made in several organs but not in the bladder. We studied the extrahypothalamic GnRH and GnRH receptor in bladder cancer epithelia, and the role of GnRH on bladder cancer cell proliferation. Material and Methods: Normal human bladder mucosa, human transitional bladder cancer tissue, and 4 bladder cancer cell lines were used. For culture media, normal or charcoal-stripped serum with exogenous GnRH of different concentrations ( 0, 10(-3), 10(-5), and 10(-7) M) were supplemented. For detection of GnRH and the GnRH receptor and its mRNAs, RNase protection assay, in situ hybridization, and immunocytochemistry were performed. Cellular proliferation was measured by hemocytometer and the cell cycle by flow cytometer. Results: GnRH and GnRH receptor mRNA expression were detected in all cancer cell lines and human bladder cancer tissues. GnRH and GnRH receptors were localized in bladder cancer epithelial cells, but the density was not even. There were no significant differences ( p > 0.05) in proliferation, and no significant change ( p > 0.05) in cell cycle with GnRH supplements compared to controls. Conclusion: The bladder epithelia produce GnRH and the GnRH receptor in both normal and malignant tissues, but GnRH does not induce proliferation or cell cycle change of bladder cancer cells. Copyright (c) 2008 S. Karger AG, Basel.