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 muscle with alpha1 adrenergic blockade, or shrinkage of the gland with 5alpha-reductase inhibitors. We recently demonstrated that alpha1-blockers, such as terazosin, induce apoptosis in prostatic cells. In this study, we 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 either 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 symptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against TGF-beta1 and TbetaRII were used to examine the immunoreactivity of TGF-beta1 and TbetaRII, respectively, in all prostate tissue sections.


RESULTS
The apoptotic index in both prostate cell populations was significantly higher following the combination treatment compared to terazosin or finasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant increase in TGF-beta1 expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in TbetaRII expression.


CONCLUSIONS
These results support the concept that induction of prostate apoptosis is a potential molecular mechanism underlying the combination effect of alpha1 blockade with 5alpha-reductase inhibitors in the effective treatment of BPH. The upregulation of TGF-beta1 implies a role for this ligand as an effector of apoptosis induction in response to alpha1-blockade or finasteride therapy of BPH patients.
Glassman
D T
DT
Division of Urology, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Chon
J K
JK
Borkowski
A
A
Jacobs
S C
SC
Kyprianou
N
N
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018120:Finasteride / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000737:chemistry; D016014:Linear Models; D008297:Male; D011224:Prazosin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D012044:Regression Analysis; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000032:analysis
D000317:Adrenergic alpha-Antagonists; D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D018120:Finasteride; C041226:Terazosin; D011224:Prazosin