APOPTOSIS AND RELATED GENES IN THE RAT VENTRAL PROSTATE FOLLOWING ANDROGEN ABLATION IN RESPONSE TO ETHANE DIMETHANESULFONATE

BACKGROUND. Following androgen withdrawal, regression of the prostate is characterized by apoptotic cell death. The molecular events governi ng this process have not been fully characterized. METHODS. Using etha ne-1,2-dimethanesulfonate (EDS) to induce androgen ablation, we invest igated the role of the Bcl-2 family members and Fas pathway in this ph enomenon. Prostates were examined from adult male rats injected with 1 00 mg/kg EDS and killed 2, 5, and 8 days later. RESULTS. Regression of the prostate was evident as a time-dependent decrease in weight. The number of apoptotic cells identified by in situ end labeling was maxim al after 5 days of treatment. There was no statistically significant c hange in the expression of Bar, Bcl-xl, Bcl-2, or p53 following androg en withdrawal. In contrast, 5 days post-EDS treatment, testosterone-re pressed prostate message (TRPM-2) and Fas-R expression were induced. T here was a decline in Fas-L levels 8 days after EDS administration. CO NCLUSIONS. This study extends previous work which has shown that andro gen withdrawal induces apoptosis in the prostate. We have shown that a lthough p53 and the Bcl-2 family members examined in this study do not seem to be important in this process, the Pas pathway may play a role in apoptosis of the ventral prostate in response to androgen ablation . Prostate 36:23-30, 1998. (C) 1998 Wiley-Liss, Inc.