I Woolveridge1, M F Taylor, F C Wu, I D Morris. 1. Division of Physiology, Pharmacology, and Toxicology, School of Biological Sciences, University of Manchester, United Kingdom. Ian.woolveridge@man.ac.uk
Abstract
BACKGROUND: Following androgen withdrawal, regression of the prostate is characterized by apoptotic cell death. The molecular events governing this process have not been fully characterized. METHODS: Using ethane-1,2-dimethanesulfonate (EDS) to induce androgen ablation, we investigated the role of the Bcl-2 family members and Fas pathway in this phenomenon. Prostates were examined from adult male rats injected with 100 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 maximal after 5 days of treatment. There was no statistically significant change in the expression of Bax, Bcl-xl, Bcl-2, or p53 following androgen withdrawal. In contrast, 5 days post-EDS treatment, testosterone-repressed prostate message (TRPM-2) and Fas-R expression were induced. There was a decline in Fas-L levels 8 days after EDS administration. CONCLUSIONS: This study extends previous work which has shown that androgen withdrawal induces apoptosis in the prostate. We have shown that although p53 and the Bcl-2 family members examined in this study do not seem to be important in this process, the Fas pathway may play a role in apoptosis of the ventral prostate in response to androgen ablation.
BACKGROUND: Following androgen withdrawal, regression of the prostate is characterized by apoptotic cell death. The molecular events governing this process have not been fully characterized. METHODS: Using ethane-1,2-dimethanesulfonate (EDS) to induce androgen ablation, we investigated the role of the Bcl-2 family members and Fas pathway in this phenomenon. Prostates were examined from adult male rats injected with 100 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 maximal after 5 days of treatment. There was no statistically significant change in the expression of Bax, Bcl-xl, Bcl-2, or p53 following androgen withdrawal. In contrast, 5 days post-EDS treatment, testosterone-repressed prostate message (TRPM-2) and Fas-R expression were induced. There was a decline in Fas-L levels 8 days after EDS administration. CONCLUSIONS: This study extends previous work which has shown that androgen withdrawal induces apoptosis in the prostate. We have shown that although p53 and the Bcl-2 family members examined in this study do not seem to be important in this process, the Fas pathway may play a role in apoptosis of the ventral prostate in response to androgen ablation.