Gonadotropin-Releasing Hormone (GnRH) and GnRH Receptor in Bladder Cancer Epithelia and GnRH Effect on Bladder Cancer Cell Proliferation

Abstract

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^–7M) 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.

Degarelix versus Goserelin plus Bicalutamide Therapy for Lower Urinary Tract Symptom Relief, Prostate Volume Reduction and Quality of Life Improvement in Men with Prostate Cancer: A Systematic Review and Meta-Analysis

“…Indeed, GnRH receptors have been identified on the epithelial and smooth muscle cells of the prostate, on the peripheral lymphocytes infiltrating the prostate, and on the bladder mucosa in both animals and in humans [22,23,24,25,26,27]. GnRH receptor blockade on these cells has been associated with the downregulation of pro-inflammatory cytokines, various growth factors and even α1-adrenoreceptors [27,28], with potential implications for smooth muscle relaxation in prostate strips and TPV reduction [29].…”

Expression of Receptors for Luteinizing Hormone-Releasing Hormone (LH-RH) in Prostate Cancers following Therapy with LH-RH Agonists

“…A potential therapeutic target is the LH-RH receptor. Recent studies have shown that LH-RH receptors are expressed on a variety of human cancer cells, including ovarian (10), endometrial (11), pancreatic (12), rectal (13), renal (14), bladder (15), and breast cancer cells (16). Several groups have also shown LH-RH receptor expression with fairly high prevalence in prostate cancer cells.…”

Contraceptive Vaccines for Wildlife: A Review

“…More troubling, however, are a variety of other issues associated with any vaccine that blocks GnRH. It has now been demonstrated that GnRH receptors exist in a variety of tissues throughout the mammalian body, including the cerebellum, 52 bladder, 53 and cerebrospinal fluid. 54 Now recognized as a form of neurotransmitter, GnRH has physiological effects throughout the central nervous system.…”