Experimental diabetes-induced regression of the rat prostate is associated with an increased expression of transforming growth factor-beta.
OBJECTIVE
Transforming growth factor-beta (TGF-beta), a potent inhibitor of cell growth, plays an important role in the androgen-dependent processes of the prostate through a complex network of growth factors. TGF-beta expression in the prostate is under negative regulatory control of androgen. As experimental diabetes causes a regression of the prostate and decrease in serum testosterone levels in rats, we examined TGF-beta alterations at the mRNA and protein levels in the diabetic rat prostate.


METHODS
The expression of TGF-beta1 and TGF-beta2 and their respective mRNAs in prostates from streptozotocin (STZ)-induced diabetic, insulin-treated diabetic and age-matched control rats were investigated, using relative multiplex RT-PCR, semi-quantitative Western blotting, and immunohistochemistry.


RESULTS
Induction of diabetes caused a significant reduction in prostatic weight and in serum testosterone levels in rats. Both mRNA and protein levels of TGF-beta1, and mRNA level of TGF-beta2 were up-regulated in the diabetic rat prostate. Insulin-treatment normalized changes observed in prostatic weight and serum testosterone levels, and reversed the alterations in the TGF-beta1 and TGF-beta2 expression at the gene transcript and protein levels to control levels. Immunohistochemical studies demonstrated that TGF-beta1 is localized to prostatic stromal cells, whereas TGF-beta2 is located in both epithelial and stromal cells.


CONCLUSIONS
These results suggest that TGF-beta1 and TGF-beta2 may be involved in the diabetes-induced regression of the prostate gland.
Ikeda
K
K
Section of Urology, Yale University School of Medicine, New Haven, Connecticut, USA.
Wada
Y
Y
Foster
H E
HE
Wang
Z
Z
Weiss
R M
RM
Latifpour
J
J
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta