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 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.
Woolveridge
I
I
Division of Physiology, Pharmacology, and Toxicology, School of Biological Sciences, University of Manchester, United Kingdom. Ian.woolveridge@man.ac.uk
Taylor
M F
MF
Wu
F C
FC
Morris
I D
ID
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051152:Clusterin; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2; D016158:Genes, p53; D006023:Glycoproteins; D008297:Male; D008698:Mesylates / Q000633:toxicity*; D018832:Molecular Chaperones; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects; D019014:fas Receptor / Q000276:immunology*
D000728:Androgens; D051152:Clusterin; D006023:Glycoproteins; D008698:Mesylates; D018832:Molecular Chaperones; D019014:fas Receptor; C002994:ethylene dimethanesulfonate