CASTRATION INDUCES APOPTOSIS IN THE VENTRAL PROSTATE BUT NOT IN AN ANDROGEN-SENSITIVE PROSTATIC ADENOCARCINOMA IN THE RAT

Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenoc arcinoma was studied during the post castration period of 14 days and compared with the ventral prostate. The mRNA expression of testosteron e repressed prostatic message-2 and tissue-type plasminogen activator in the Dunning tumor and in the ventral prostate was analyzed by North ern blot experiments and immunohistochemical procedures. The degree of endonuclease degraded genomic DNA was examined by gel electrophoresis . Apoptotic tumor epithelial cells were identified with in situ end la beling. Epithelial cells incorporating bromodeoxyuridine (BrdUrd) afte r castration in the ventral prostate and the Dunning tumors were local ized with immunostaining. Androgen ablation resulted in an induction o f testosterone repressed prostatic message-2 and tissue-type plasminog en activator transcripts in the normal prostate with a peak at approxi mately 2 to 5 days post castration. These transcript levels in the Dun ning prostatic tumors did not show any induction during the same perio d. Immunohistochemical staining for sulfated glycoprotein-2 and tissue -type plasminogen activator confirmed this difference between the tumo r tissue and the ventral prostate at the transcriptional level. The de termination of DNA integrity showed similar results in that the degree of DNA fragmentation in the tumor was much lower than the initial and marked degradation of DNA in the ventral prostate. The number of in s itu end labeled epithelial tumor cells were not increased by castratio n. BrdUrd immunodetection showed that castration induced an initial in crease in the number of BrdUrd-positive epithelial cells in the ventra l prostate. In the tumors, castration resulted in a decrease in BrdUrd -positive epithelial cells. It was concluded that in the androgen-sens itive prostatic Dunning R3327 PAP adenocarcinoma, the biochemical casc ade leading to apoptosis is not activated by androgen withdrawal, as i n the ventral prostate.