Ultrastructural and biochemical observations on the early changes in apoptotic epithelial cells of the rat prostate induced by castration

The present study describes the sequential ultrastructural changes in the a poptotic cells of the rat ventral and dorsal prostates during the early per iod of 1-3 days postcastration. The major morphological changes include: (1 ) condensation of heterochromatin along the nuclear envelope and fragmentat ion into crescent-shaped micronuclei; (2) formation of membrane-bound cytop lasmic spherical bodies, which contain various organelles and micronuclei, within the apoptotic cells; (3) formation of non-membrane-bound autolytic v acuoles by autolysis of cytoplasm; (4) focal rupture of outer mitochondrial membrane; and (5) phagocytosis of the fragmented cytoplasmic spherical bod ies and apoptotic cells by macrophages. The occurrence of both cytoplasmic apoptotic bodies and autolytic vacuoles in apoptotic cells suggests that th e cytoplasm of the apoptotic cells could be destroyed by different means. T he responsiveness of different prostatic lobes to androgen withdrawal and t he time course of the transitory apoptotic activity in different lobes were analyzed by counting the indices of the TUNEL-labeled apoptotic cells agai nst the postcastration periods. The results showed that the ventral lobe re sponded more rapidly to castration than the lateral and dorsal lobes. The d orsal lobe was the slowest in response to castration among the three lobes. Analysis of protease activities by zymography has identified two Ca2+-inde pendent proteases of apparent MW 20 and 24 kDa (expressed in both ventral a nd dorsolateral lobes), and one Ca2+-dependent protease of MW 66.5 kDa (exp ressed only in the dorsolateral lobe) which became activated at day 3 postc astration. Their expression patterns were different from that of CPP-3 in t he castrated prostates, suggesting that the activated proteases were enzyme s other than CPP-3. The association of their highest activities with the ma ximum apoptotic activity at day 3 postcastration and also their loss of act ivity at day 15 suggest that these protease activities might be related to apoptosis or glandular involution.