Transforming growth factor beta 1 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 alpha 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-beta 1Neo) transduction of transforming growth factor beta 1 (TGF-beta 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-beta 1-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-beta 1 transduced MPRs than BAG alpha 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.
Yang
G
G
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Timme
T L
TL
Park
S H
SH
Wu
X
X
Wyllie
M G
MG
Thompson
T C
TC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D017292:Doxazosin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000473:pathology / Q000503:physiopathology*; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D016212:Transforming Growth Factor beta; D017292:Doxazosin