G. Yang et al., TRANSFORMING-GROWTH-FACTOR BETA-1 TRANSDUCED MOUSE PROSTATE RECONSTITUTIONS .2. INDUCTION OF APOPTOSIS BY DOXAZOSIN, The Prostate, 33(3), 1997, pp. 157-163
BACKGROUND. To study the possible relationship between adrenergic acti
vities and the alpha 1-adrenoceptor antagonist, on prostatic growth in
vivo using a mouse model for BPH. METHODS. The mouse prostate reconst
itution (MPR) model system with retroviral (BabeTGF-beta 1Neo) transdu
ction of transforming growth factor beta 1 (TGF-beta 1) was used to in
duce focally hyperplastic BPH-like lesions and increase the number of
catecholaminergic neurons. The mice were treated with daily intraperit
oneal injections of doxazosin (3 mg/kg). RESULTS. Doxazosin caused a s
ignificant reduction in the wet weight of BabeTGF-beta 1-infected MPRs
. The percent of PCNA-positive epithelial cells was similar in the dox
azosin-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 d
oxazosin group vs. 3.1 for control group, P < 0.05). The doxazosin-ind
uced apoptosis was more apparent in TGF-beta 1 transduced MPRs than BA
G alpha control MPRs, and was not seen in the prostates of the adult m
ale mice into which the MPRs were engrafted. CONCLUSIONS. Our data dem
onstrate a novel and potentially important biological activity of doxa
zosin in vivo in this mouse model of BPH. (C) 1997 Wiley-Liss, Inc.