Role of calcium in the programmed death of rat prostatic glandular cells.

By using a newly developed and validated rat ventral prostatic organ culture system in which prostatic glandular cells can be induced to undergo programmed cell death, the role of an elevation in the intracellular free Ca2+ concentration in this death process was studied. By using this organ culture system, ventral prostatic glandular epithelial cells can be maintained in culture for a period of more than 14 days with a low daily rate of cell death (i.e., approximately 5% die per day) if androgen is included in the media. In contrast, if androgen is not included in the media, the daily rate of prostatic glandular cell death increases approximately 3-fold (i.e., approximately 15% die per day). With this organ culture system it has been demonstrated that the daily rate of programmed death of the glandular epithelial cells can be shifted from 5% to 15% of the cells dying per day when testosterone and 10 microM of the Ca2+ ionophore A23187 are both present in the media. Thus, when the intracellular free Ca2+ is elevated within prostatic cells by means of ionophore treatment, the daily rate of glandular cell death in the presence of testosterone is identical to that induced when testosterone is not present in the media. If the organ cultures are maintained in media lacking testosterone but containing 10 microM of the Ca2+ channel blocker nifedipine to inhibit elevations in the intracellular free Ca2+ derived from the extracellular pools, the rise in the daily rate of cell death from 5 to 15% of the cells dying per day induced by androgen ablation can be inhibited by approximately 70%. These results suggest that an increase within prostatic glandular cells in their intracellular free Ca2+ derived from extracellular Ca2+ pools is a critical early event involved in triggering the subsequent process of programmed cell death (i.e., specifically DNA fragmentation) in these cells following androgen ablation.