Effect on the carcinogenesis of male rat bladder cancer of antiandrogen and 5_<alpha>-reductase inhibitor

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It has been reported that blocking of androgen inhibits bladder carcinogenesis in male rats. However, the mechanism of action of androgen in bladder carcinogenesis is not known. To investigate this problem, we designed the following study using three antiandrogen drugs that have different mechanisms.We administered 0.05% BBN orally to 117 Wistar rats for 10 weeks, and divided them into 7 treatment groups (control, surgical castration, finasteride, LH-RH agonist, flutamide, LH-RH agonist + finasteride and LH-RH agonist + flutamide). Rats were cystectomized in the 21st week and speciments were examined histopathologically. Results demonstrated that surgical castration and LH-RH agonist treatment (three groups) reduced the incidence of carcinoma significantly and that surgical castration had a greater inhibitory effect than the LH-RH agonist. These observations suggest that androgen acts directly on the bladder mucosa. On the other hand, LH-RH agonist + flutamide showed greater inhibition than LH-RH agonist + finasteride, suggesting that testosterone combines directly with androgen receptor without conversion to DHT.We also investigated the presence of androgen receptors in rat and mouse bladder mucosa using monclonal and polyclonal antibodies and western blotting after homogenation. Results confirmed the existence of monoclonal antibody overlapping nuclei in mouse and rat bladder mucosa, as in accessory sex organs, and recognition of a protein corresponding to the molecular weight of the androgen receptor.