Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-β expression in benign prostatic hyperplasia

BACKGROUND. Medical treatment of benign prostatic hyperplasia (BPH) targets relief of symptoms by causing either relaxation of the prostatic smooth muscle with α₁ adrenergic blockade, or shrinkage of the gland with 5α-reductase inhibitors. We recently demonstrated that α₁-blockers, such as terazosin, induce apoptosis in prostatic cells. In this study, we examined the combined effect of finasteride and terazosin on the rate of apoptosis and cellular proliferation to investigate their potential synergy at the cellular level. METHODS. Prostate specimens were obtained from men who were treated with either finasteride (n=24), terazosin (n =42), or combination therapy (n =10) for varying time periods (1 week to 36 months) for the relief of the symptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against TGF-β₁ and TβRII were used to examine the immunoreactivity of TGF-β₁ and TβRII, respectively, in all prostate tissue sections. RESULTS. The apoptotic index in both prostate cell populations was significantly higher following the combination treatment compared to terazosin or finasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant increase in TGF-β₁ expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in TβRII expression. CONCLUSIONS. These results support the concept that induction of prostate apoptosis is a potential molecular mechanism underlying the combination effect of α₁ blockade with 5α-reductase inhibitors in the effective treatment of BPH. The upregulation of TGF-β₁ implies a role for this ligand as an effector of apoptosis induction in response to α₁-blockade or finasteride therapy of BPH patients.