Transforming growth factor β1 transduced mouse prostate reconstitutions: II. Induction of apoptosis by doxazosin

BACKGROUND. To study the possible relationship between adrenergic activities and the pathogenesis of benign prostatic hyperplasia (BPH), we tested the effect of doxazosin, an α1-adrenoceptor antagonist, on prostatic growth in vivo using a mouse model for BPH. METHODS. The mouse prostate reconstitution (MPR) model system with retroviral (BabeTGF-β1Neo) transduction of transforming growth factor beta 1 (TGF-β1) was used to induce focally hyperplastic BPH-like lesions and increase the number of catecholaminergic neurons. The mice were treated with daily intraperitoneal injections of doxazosin (3 mg/kg). RESULTS. Doxazosin caused a significant reduction in the wet weight of BabeTGF-β1-infected MPRs. The percent of PCNA-positive epithelial cells was similar in the doxazosin-treated and water only, control groups. There was a significant increase in the number of epithelial cells undergoing programmed cell death, apoptosis, in the doxazosin group (apoptotic index = 4.7 for doxazosin group vs. 3.1 for control group, P < 0.05). The doxazosin-induced apoptosis was more apparent in TGF-β1 transduced MPRs than BAGα control MPRs, and was not seen in the prostates of the adult male mice into which the MPRs were engrafted. CONCLUSIONS. Our data demonstrate a novel and potentially important biological activity of doxazosin in vivo in this mouse model of BPH.