Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression.
BACKGROUND
Prostatic atrophy has been documented histologically as a consequence of finasteride action on human hyperplastic prostates. An increase in apoptotic rates has also been reported in androgen-deprived hyperplastic prostates. Transforming growth factor beta (TGF-beta) signaling is implicated in apoptotic cell death. TGF-betas have been detected in normal and diseased human prostate. In the normal prostate, TGF-beta acts as a predominantly negative growth regulator. TGF-beta signaling receptors TbetaRI and TbetaRII have been shown to be negatively regulated by androgens.


METHODS
We studied the histological changes in 9 selected finasteride-treated patients with benign prostatic hyperplasia (BPH), and analyzed the levels of expression and localization of TGF-beta receptor types TbetaRI and TbetaRII in these patients as compared to selected BPH controls.


RESULTS
The prostatic epithelial compartment seemed to be a primary target site for finasteride action, since we observed moderate to severe glandular atrophy after 4-6 months of treatment. TGF-beta receptors were upregulated in treated cases. We assessed a twofold increase in TbetaRII mRNA levels in treated cases as compared to controls. An increase in both TbetaRI and TbetaRII at the protein level by immunostaining was observed, which also provided a helpful means for detecting glands undergoing regression.


CONCLUSIONS
We conclude that finasteride may modulate the TGF-beta signaling system to promote changes leading to apoptosis of epithelial cells and prostatic glandular atrophy.
Sáez
C
C
Department of Pathology, Hospital Universitario Virgen del Rocío, Seville, Spain. dsegura@hvr.sas.cica.es
González-Baena
A C
AC
Japón
M A
MA
Giráldez
J
J
Segura
D I
DI
Miranda
G
G
Rodríguez-Vallejo
J M
JM
González-Esteban
J
J
Torrubia
F
F
D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000503:physiopathology; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D018120:Finasteride