LOBE-SPECIFIC APOPTOTIC CELL-DEATH IN RAT PROSTATE AFTER ANDROGEN ABLATION BY CASTRATION

It is well established that androgens are central to regulation of the growth of the mammalian prostate gland. Conversely, androgen deprivat ion by castration induces rapid cell death in the ventral prostate via an apoptotic mechanism. To date, most studies of cell death in the ro dent prostate have focused on the ventral lobe, with little attention directed to the dorsal and lateral lobes. The results presented herein demonstrate that cell death in the rat prostate gland caused by castr ation is lobe specific. In particular, castration caused decreases in wet weights and protein contents of all three prostatic lobes, but the se events were more rapid and profound in the ventral than in the dors al and lateral lobes. Reduced epithelial cell size was apparent in the three lobes as well. However, castration resulted in loss of DNA cont ent in the ventral lobe only. To confirm this finding, and to examine apoptosis of individual cells, we used in situ labeling of fragmented DNA, supported by biochemical analysis of DNA integrity in agarose gel s. With both approaches, significant cell death in response to castrat ion was seen in the ventral lobe but not the dorsal and lateral lobes. Taken together, these results clearly indicate that there are lobe-sp ecific differences in the response of the rat prostate to androgen abl ation by castration, with apoptotic cell death occurring in the ventra l lobe of the prostate but to a far lesser extent, if at all, in the d orsal and lateral lobes. Moreover, castration caused apoptotic death o f both epithelial and stromal cells of the ventral prostate, with thes e cells dying throughout the ductal network of the ventral prostate ra ther than being restricted to a particular region. We suggest that lob e-specific differences in androgen responsiveness in the rat prostate may provide an appropriate model for the study of androgen-independent prostatic cell survival during tumor progression.