Promoting effects and mechanisms of action of androgen in bladder carcinogenesis in male rats
- PMID: 9129932
- DOI: 10.1159/000474484
Promoting effects and mechanisms of action of androgen in bladder carcinogenesis in male rats
Abstract
Objective: It has been reported that blocking of testosterone production inhibits bladder carcinogenesis in various animal models. We investigated how testosterone acts on rat bladder carcinogenesis using an antiandrogen, flutamide, and a 5 alpha-reductase inhibitor, finasteride.
Methods: Experiment 1: we administered 0.05% BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] orally to 117 Wistar rats for 10 weeks, divided them into seven groups-control, surgical castration, finasteride (2 mg/kg), luteinizing hormone releasing hormone (LH-RH) agonist (1 mg/kg) flutamide (50 mg/kg), LH-RH agonist plus finasteride, and LH-RH agonist plus flutamide-, and then cystectomized them to investigate the incidence of bladder cancer on week 21; experiment 2: we administered 0.05% BBN to 154 Wistar rats for 7 weeks, divided them into seven groups-control, finasteride 2, 4, and 8 mg/kg, and flutamide 50, 100, and 200 mg/kg-, and then we cystectomized them to investigate the dose-dependent influence on bladder carcinogenesis of these drugs on week 20, and experiment 3: we investigated the presence of androgen receptors in rat and mouse normal bladder mucosa using a monoclonal antibody.
Results and conclusions: Experiment 1: Surgical castration and LH-RH agonist treatment significantly reduced the occurrence of carcinomas. There was no significant additive effect of coadministered finasteride or flutamide with LH-RH agonist. Finasteride or flutamide monotherapy showed no statistically significant effects on the results of experiment 1 at the doses used. Experiment 2: Flutamide showed a dose-dependent effect on reducing the number of rats with bladder cancer, and at a dosis of 200 mg/kg twice a week, the difference was statistically significant when compared with the control group, whereas finasteride had no statistically significant suppressing effect at any dose. Experiment 3: Mouse and rat bladder urothelium expressed the androgen receptor. Our results indicate that testosterone itself might have a more potent action on bladder carcinogenesis rather than its converting form, 5 alpha-dihydrotestosterone.
Similar articles
-
[Effects of androgen regulation system on bladder carcinogenesis in male mice].Nihon Hinyokika Gakkai Zasshi. 1995 Nov;86(11):1666-72. doi: 10.5980/jpnjurol1989.86.1666. Nihon Hinyokika Gakkai Zasshi. 1995. PMID: 8551710 Japanese.
-
Effect of turosteride, a 5 alpha-reductase inhibitor, on the Dunning R3327 rat prostatic carcinoma.Prostate. 1997 Feb 1;30(2):85-91. doi: 10.1002/(sici)1097-0045(19970201)30:2<85::aid-pros3>3.0.co;2-j. Prostate. 1997. PMID: 9051146
-
[Effects of luteinizing hormone-releasing hormone agonist on bladder carcinogenesis in male rats].Nihon Hinyokika Gakkai Zasshi. 1992 Sep;83(9):1452-8. doi: 10.5980/jpnjurol1989.83.1452. Nihon Hinyokika Gakkai Zasshi. 1992. PMID: 1434288 Japanese.
-
Mechanism of action and pure antiandrogenic properties of flutamide.Cancer. 1993 Dec 15;72(12 Suppl):3816-27. doi: 10.1002/1097-0142(19931215)72:12+<3816::aid-cncr2820721711>3.0.co;2-3. Cancer. 1993. PMID: 8252497 Review.
-
Hormone ablation therapy: lightening the load for today's prostate cancer patient.Urol Nurs. 2007 Feb;27 Suppl:3-11. Urol Nurs. 2007. PMID: 17474637 Review.
Cited by
-
Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen.Transl Oncol. 2013 Jun 1;6(3):244-55. doi: 10.1593/tlo.13247. Print 2013 Jun. Transl Oncol. 2013. PMID: 23730403 Free PMC article.
-
Androgen receptor mRNA expression is a predictor for recurrence-free survival in non-muscle invasive bladder cancer.BMC Cancer. 2019 Apr 8;19(1):331. doi: 10.1186/s12885-019-5512-9. BMC Cancer. 2019. PMID: 30961575 Free PMC article.
-
Androgen Receptor: Evaluation and Correlation with Recurrence and Clinicopathological Parameters in Papillary Urothelial Carcinomas of the Urinary Bladder.Cureus. 2020 Jan 20;12(1):e6715. doi: 10.7759/cureus.6715. Cureus. 2020. PMID: 32104638 Free PMC article.
-
Androgen receptor decreases the cytotoxic effects of chemotherapeutic drugs in upper urinary tract urothelial carcinoma cells.Oncol Lett. 2013 Apr;5(4):1325-1330. doi: 10.3892/ol.2013.1140. Epub 2013 Jan 18. Oncol Lett. 2013. PMID: 23599788 Free PMC article.
-
Role of androgen receptor expression in non-muscle-invasive bladder cancer: a systematic review and meta-analysis.Histol Histopathol. 2020 May;35(5):423-432. doi: 10.14670/HH-18-189. Epub 2019 Dec 5. Histol Histopathol. 2020. PMID: 31803932 Review.
MeSH terms
Substances
LinkOut - more resources
Medical