Urologia Internationalis
Original Paper
Gonadotropin-Releasing Hormone (GnRH) and GnRH Receptor in Bladder Cancer Epithelia and GnRH Effect on Bladder Cancer Cell ProliferationBahk J.Y.a · Kim M.O.b · Park M.S.b · Lee H.Y.b · Lee J.-H.c · Chung B.C.d · Min S.K.eaDepartment of Urology, Gyeongsang National University Medical School, bDivision of Life Science, College of Natural Sciences and Applied Life Science (Brain Korea 21), Gyeongsang National University, and cDepartment of Pathology, Gyeongsang National University Medical School, Jinju; dBioanalysis and Biotransformation Research Center, KIST, and eDepartment of Urology, National Police Hospital, Seoul, Korea
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Article / Publication Details
Received: September 14, 2006
Accepted: February 12, 2007
Published online: June 27, 2008
Issue release date: June 2008
Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 2
ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)
For additional information: https://www.karger.com/UIN
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.
© 2008 S. Karger AG, Basel
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References
- Morisue K, Yamanaka N, Eto H, Kamidonu S, Nishimura R: Ectopic production of HCG beta by bladder carcinoma in vitro and in vivo. Nippon Hinyokika Gakkai Zasshi 1996;87:643–649.
-
Moreville M, Fritz RW, Mulholland SG: Enhancement of the bladder defense mechanism by an exogenous agent. J Urol 1993;130:607–609.
- Vaidyanathan S, McCreavy DT, McDicken IW, Soni BM, Mansour P, Wlodarski B, Carron JA, Fraser WD, Singh G, Sett P, Gallagher JA: Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury. Spinal Cord 1999;37:760–764.
- Ponglowhapan S, Church DB, Scaramuzzi RJ, Khalid M: Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs. Theriogenology 2007;67:353–366.
- Reichler IM, Barth A, Piche CA, Jochle W, Roos M, Hubler M, Arnold S: Urodynamic parameters and plasma LH/FSH in spayed beagle bitches before and 8 weeks after GnRH depot analogue treatment. Theriogenology 2006;66:2127–2136.
- Welle MM, Reichler IM, Barth A, Forster U, Sattler U, Arnold S: Immunohistochemical localization and quantitative assessment of GnRH-, FSH-, and LH-receptor mRNA expression in canine skin: a powerful tool to study the pathogenesis of side effects after spaying. Histochem Cell Biol 2006;126:527–535.
- Hotakainen K, Lintula S, Stenman J, Rintala E, Lindell O, Stenman UH: Detection of messenger RNA for the beta-subunit of chorionic gonadotropin in urinary cells from patients with transitional cell carcinoma of the bladder by reverse transcription-polymerase chain reaction. Int J Cancer 1999;84:304–308.
- Messing EM: Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma. Cancer Res 1990;50:2530–2537.
- Ozaki K, Sukata T, Yamamoto S, Uwagawa S, Seki T, Kawasaki H, Yoshitake A, Wanibuchi H, Koide A, Mori Y, Fukushima S: High susceptibility of p53(+/–) knockout mice in N-butyl-N-(4-hydroxybutyl) nitrosamine urinary bladder carcinogenesis and lack of frequent mutation in residual allele. Cancer Res 1998;58:3806–3811.
- Ruck A, Paulie S: The epidermal growth factor receptor is involved in autocrine growth of human bladder carcinoma cell lines. Anticancer Res 1997;17:1925–1931.
- Visvanathan KV, Pocock RD, Summerhayes IC: Preferential and novel activation of H-ras in human bladder. Oncogene Res 1988;3:77–86.
- Silverman AJ, Krey LC: The luteinizing hormone releasing hormone (LHRH) neuronal networks of the guinea pig brain. I. Intra-and extra hypothalamic projections. Brain Res 1978;157:233–246.
- Naor Z, Clayton RN, Catt KJ: Characterization of gonadotropin-releasing hormone receptors in cultured rat pituitary cells. Endocrinology 1980;107:1144–1152.
- Gibbons JM, Mitnick M, Chieffo V: In vitro biosynthesis of TSH- and LH-releasing factors by the human placenta. Am J Obstet Gynecol 1975;121:127–131.
- Bahk JY, Hyun JS, Chung SH, Kim MO, Choi WS: Stage specific identification of the expression of GnRH mRNA and localization of the GnRH receptor in mature rat and adult human testis. J Urol 1995;154:1958–1961.
- Li SP, Park MS, Bahk JY, Kim MO: Chronic nicotine and smoking exposure decreases GABA(B1) receptor expression in the rat hippocampus. Neurosci Lett 2002;334:135–139.
- Chai L, Choi WS, Ronnekleiv OK: Maternal cocaine treatment alters dynorphin and enkephalin mRNA expression in brains of fetal rhesus macaques. J Neurosci 1997;17:1112–1121.
- Kim MO, Lee YK, Choi WS, Kim JH, Hwang SK, Lee BJ, Kang SG, Kim K, Baik SH: Prolonged ethanol intake increases D2 dopamine receptor expression in the rat brain. Mol Cells 1997;7:682–687.
-
Li SP, Park MS, Yoon H, Rhee KH, Bahk JY, Lee JH, Park JS, Kim MO: Differential distribution of GABA(B1) and GABA(B2) receptor mRNAs in the rat brain. Mol Cells 2003;31:40–47.
External Resources
- Yamamoto M, Harm SC, Grasser WA, Thiede MA: Parathyroid hormone-related protein in the rat urinary bladder a smooth muscle relaxant produced locally in response to mechanical stretch. Proc Natl Acad Sci USA 1992;89:5326–5330.
- Grammatico D, Grignon DJ, Eberwein P, Shepherd RR, Hearn SA, Walton JC: Transitional cell carcinoma of the renal pelvis with choriocarcinomatous differentiation. Immunohistochemical and immunoelectron microscopic assessment of human chorionic gonadotropin production by transitional cell carcinoma of the urinary bladder. Cancer 1993;71:1835–1841.
-
Yohimoto Y, Wolfsen AF, Odell WD: Human chorionic gonadotrophin-like substance in nonendocrine tissues of normal subjects. Science 1977;197:575–577.
External Resources
- Heyderman E, Chapman DV, Richardson TC, Calvert I, Rosen SW: Human choronic gonadotrophin and human placental lactogen in extragonadal tumors: an immununoperoxidase study of ten non-germ cell neoplasms. Cancer 1985;56:2674–2682.
- Saez S, Martin PM: Evidence of estrogen receptors in the trigone area of the human urinary bladder. J Steroid Biochem 1981;15:317–320.
- Bodker A, Balslev E, Iversen HG, Meyhoff HH, Andersson KE: Estrogen receptors in the human male bladder, prostatic urethra and prostate in prostatic cancer and benign prostatic hyperplasia. Scand J Urol Nephrol 1999;33:237–242.
- Shibata MA, Shirai T, Asakawa E, Hirose M, Fukushima S: Inhibition by dehydroepiandrosterone of butylated hydroxyanisole (BHA) promotion of rat-bladder carcinogenesis and enhancement of BHA-induced forestomach hyperplasia. Int J Cancer 1993;53:819–823.
- Shirai T, Yamamoto A, Iwasaki S, Tamano S, Masui T: Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis(2-oxopropyl) amine and followed by testosterone propionate with or without high-fat diet. Carcinogenesis 1991;12:2169–2173.
- Cunha GR, Lung B: The importance of stroma in morphogenesis and functional activity of urogenital epithelium. In Vitro 1979;15:50–71.
- Huggins CB: The formation of bone under the influence of epithelium of the urinary tract. Clin Orthop 1968;59:7–19.
- Johnson FR, McMinn MR: Transitional epithelium and osteogenesis. J Anat 1956;90:106–116.
- Bahk JY, Hyun JS, Lee H, Kim MO, Cho GJ, Lee BH, Choi WS: Expression of GnRH and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells. Urol Res 1998;26:259–264.
Article / Publication Details
Received: September 14, 2006
Accepted: February 12, 2007
Published online: June 27, 2008
Issue release date: June 2008
Number of Print Pages: 8
Number of Figures: 5
Number of Tables: 2
ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)
For additional information: https://www.karger.com/UIN
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