Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta 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 mu scle with alpha (1) adrenergic blockade, or shrinkage of the gland with 5 a lpha -reductase inhibitors. We recently demonstrated that alpha (1)-blocker s, such as terazosin, induce apoptosis in prostatic cells. In this study, w e 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 ei ther 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 sy mptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against T GF-beta (1) and T beta RII were used to examine the immunoreactivity of TGF -beta (1) and T beta RII, respectively, in all prostate tissue sections. RESULTS. The apoptotic index in both prostate cell populations was signific antly higher following the combination treatment compared to terazosin or f inasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant inc rease in TGF-beta (1) expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in T beta RII e xpression. CONCLUSIONS. These results support the concept that induction of prostate a poptosis is a potential molecular mechanism underlying the combination effe ct of alpha (1) blockade with 5 alpha -reductase inhibitors in the effectiv e treatment of BPM. The upregulation of TGF-beta (1) implies a role for thi s ligand as an effector of apoptosis induction in response to al-blockade o r finasteride therapy of BPH patients. Prostate 46:45-51, 2001. (C) 2001 Wi ley-Liss, inc.