Successive waves of apoptosis in the rat prostate after repeated withdrawal of testosterone stimulation

In rats with castration-induced ventral prostatic atrophy, testosterone treatment resulted in reconstitution of the normal weight and histological structure of the gland within 10 d. Subsequent withdrawal of the hormone was followed by rapid involution, which was effected by a combination of extensive loss of epithelial cells by apoptosis and decrease in the size of the cells that remained. The wave of apoptotic deletion was similar to that accompanying the initial involution after castration, and in both cases the rate of apoptosis fell to very low levels by 20 d. Two further consecutive episodes of involution produced by sequential administration and withdrawal of testosterone were also accompanied by similar waves of apoptosis. The results provide quantitative evidence supporting suggestions that apoptosis may be of major kinetic significance in the involution of endocrine-dependent glandular tissues. The majority of the epithelial cells remaining after the completion of involution were able to survive continuing androgen deprivation, but with renewed testosterone stimulation they repeatedly generated populations that once again responded to withdrawal with massive cellular death. The factors determining the selective susceptibility of individual cells in these populations clearly merit investigation.