Testosterone regulates levels of cystic fibrosis transmembrane regulator, adenylate cyclase, and cAMP in the seminal vesicles of orchidectomized rats

Abstract

Secretions of chloride (Cl−)- and bicarbonate (HCO3−)-rich fluid by the seminal vesicles could involve cystic fibrosis transmembrane regulator (CFTR), which activity can be stimulated by cAMP generated from the reaction involving adenylate cyclase (AC). In this study, we investigated levels of CFTR, AC, and cAMP in the seminal vesicles under testosterone influence. Orchidectomized adult male rats received 7-day treatment with 125 or 250 μg/kg/day of testosterone with or without flutamide or finasteride. At the end of the treatment, animals were sacrificed and seminal vesicles were harvested for analyses of CFTR and AC protein expression level by Western blotting. Distribution of CFTR and AC in seminal vesicles was observed by immunohistochemistry. Levels of cAMP and dihydrotestosterone in seminal vesicle homogenates were measured by ELISA. Cystic fibrosis transmembrane regulator, AC, and cAMP levels increased with increasing doses of testosterone (P < 0.05 compared to nontreated orchidectomized rats). Cystic fibrosis transmembrane regulator and AC were expressed at the apical membrane of the epithelium lining the seminal vesicle lumen with higher expression levels observed in testosterone-treated rats than in non-treated orchidectomized rats (P < 0.05). The inhibitory effects of flutamide or finasteride on these parameters were greater in 250 μg/kg/day testosterone-treated rats than their effects in 125 μg/kg/day testosterone-treated rats. Higher dihydrotestosterone levels were observed in seminal vesicle homogenates after treatment with 250 μg/kg/day than with 125 μg/kg/day of testosterone (P < 0.05). Increased levels of CFTR, AC, and cAMP in seminal vesicles might contribute toward an increase in Cl− and HCO3− concentrations in the seminal fluid as reported under testosterone influence.