Expression of Transforming Growth Factor-β in the Rat Ventral Prostate during Castration-Induced Programmed Cell Death

Abstract

Castration-induced androgen deprivation leads to the activation of the programmed death of the androgen-dependent prostatic epithelial cells in the rat ventral prostate. In order to identify potential mediators of this programmed cell death, the expression of transforming growth factor-.beta. (TGF.beta.) in the rat ventral prostate was studied, after castration induced-androgen withdrawal. Steady state levels of TGF.beta. mRNA were determined by Northern blot analysis and compared with mRNA levels for prostatein C3, the major androgen-dependent secretory protein of ventral prostate and also with mRNA levels for TRPM-2, a gene that is specifically expressed during castration induced prostatic cell death. Within the first day after castration there was a dramatic increase in the levels of TGF.beta. mRNA in the ventral prostate (.apprx. 10-fold) and by 4 days after castration TGF.beta. mRNA was maximally expressed (.apprx.40-fold increase), by which time the androgen-dependent C3 secretory protein mRNA transcripts have diminished to undetectable levels. Androgen administration to 4-day castrated rats led to a marked decrease in TGF.beta. mRNA to a level comparable to its constitutive expression obtained in the intact control animals, indicating that expression of TGF.beta. in the rat ventral prostate is under negative androgenic regulation. The transcript levels encoding TRPM-2 initially increased 10-fold within the first day after castration and by day 4 post castration there was a dramatic increase (.apprx.50-fold) which correlated well with the maximal rate of cell death of the androgen-dependent prostatic epithelial cells. These results suggest a temporal correlation between the expression of TGF.beta. transcripts and the activation of programmed cell death in the rat ventral prostate after castration-induced androgen withdrawal.