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

✍ Scribed by Yang, Guang; Timme, Terry L.; Park, Sang Hee; Wu, Xiuyin; Wyllie, Michael G.; Thompson, Timothy C.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 285 KB
• Volume: 33
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19971101)33:3<157::aid-pros2>3.0.co;2-g

✦ Synopsis

BACKGROUND.

To study the possible relationship between adrenergic activities and the pathogenesis of benign prostatic hyperplasia (BPH), we tested the effect of doxazosin, an ␣1-adrenoceptor antagonist, on prostatic growth in vivo using a mouse model for BPH. METHODS. The mouse prostate reconstitution (MPR) model system with retroviral (BabeTGF-␤1Neo) transduction of transforming growth factor beta 1 (TGF-␤1) 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-␤1infected MPRs. The percent of PCNA-positive epithelial cells was similar in the doxazosintreated 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 doxazosininduced apoptosis was more apparent in TGF-␤1 transduced MPRs than BAG␣ 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.