Characterization of castration-induced cell death in the rat prostate by immunohistochemical localization of cathepsin D.

Activities of cathepsin D (EC 3.4.23.5) were determined in three lobes of the prostate during their involution by both biochemical and immunohistochemical procedures. The activity of cathepsin D in noncastrated rats was 0.9 +/- 0.2 (mean +/- SE) 5.7 +/- 0.6, and 13.1 +/- 0.8 units/mg protein for the ventral, lateral, dorsal lobes, respectively. Following castration, there was a significant increase in enzymatic activity in all three lobes within 2-3 days. In the ventral lobe, the activity peaked in 5 days to 6.2 +/- 0.9 units/mg protein and declined slightly thereafter. In the lateral and dorsal lobes, the activity remained elevated (14-20 units/mg protein) throughout the postcastration period studied. Immunohistochemical staining of cathepsin D was localized in the cytoplasm of prostatic epithelial cells as fine discrete lysosomal granules. These granules were larger and more abundant in the dorsal and lateral lobes than in the ventral lobe and were not detected in prostatic stromal cells and seldom in the luminal fluid. Castration resulted in an immediate increase in the size and number of these granules in the epithelial cells, followed by a sudden further increase in cathepsin D staining in some but not all epithelial cells. Lysosomal granules gradually coalesced in these cells to form large vacuoles that fit the characteristic description of apoptotic bodies. Finally, after day 7 postcastration, collapse and disintegration of the entire glandular structure was noted. Using this procedure to localize cathepsin D as a tool, we were able to follow the morphological events of prostatic cell death during castration-induced involution in the rat at the light microscopic level.