Immunocytochemical localization of cathepsin D in rat ventral prostate: Evidence for castration‐induced expression of cathepsin D in basal cells

Abstract

Cathepsin D (EC3.4.23.5) is an aspartyl endopeptidase involved in lysosomal proteolysis. Its functional role is uncertain. This study was undertaken to determine the cellular and subcellular distribution of cathepsin D in the normal rat ventral prostate and its possible role in the castration-induced atrophy of the gland. Cathepsin D was localized immunohistochemically to perinuclear lysosomes in secretory cells, in capillary endothelial cells, and, occasionally, in stromal cells of the untreated animal. Castration resulted in an increased number of cathepsin D-positive cells in the stroma within 24 hr. By 48 hr after castration autophagolysosomes formed in secretory cells and apoptotic bodies appeared in the epithelium. Although apoptotic bodies generally contained immunoreactive cathepsin D, a subpopulation of larger apoptotic bodies, which commonly rested on the basement membrane and contained multiple inclusions, were more variable in cathepsin D expression. The induction of cathepsin D in dendritic cells basally oriented in the epithelium was noted at 4 days of castration. These cells had a phagocytic phenotype, were distributed periodically along the basement membrane, and were not found in ductal epithelia. Treatment with actinomycin D or hydrocortisone to reduce the rate of regression of the ventral prostate blocked the appearance of these cathepsin D-positive, basally oriented epithelial cells. Our data indicate that this cathepsin D-positive, phagocytic cell differentiates from a cell resident in the prostatic epithelium. We suggest that it differentiates from basal cells in the secretory tubuloalveolar portion of the gland and that it is involved in the destruction of regressed secretory cells.

Localization and Molecular Heterogeneity of Sulfated Glycoprotein-2 (Clusterin) among Ventral Prostate, Seminal Vesicle, Testis, and Epididymis of Rats1

“…SGP-2 staining became associated with large rounded vacuoles. Morphologically, these SGP-2-positive, intracellular vacuoles fit the typical description of autophagic vacuoles and/or secondary lysosomes seen to form in other tissues undergoing castration-induced regression [30,31]. Increased autophagic and heterophagic vacuole formation by caput principal cells in response to orchiectomy has been reported, supporting our concept that the SGP-2-positive vacuoles could represent autophagic vacuoles and/or secondary lysosomes [29].…”

A Comparison of the Effects of Testicular Maturation and Aging on the Stage-Specific Expression of CP-2/Cathepsin L Messenger Ribonucleic Acid by Sertoli Cells of the Brown Norway Rat1

“…This suggestion was consistent with previous observations that expression of other members of the cathepsin family of enzymes are up-regulated during apoptosis and that loss of spermatogenic cells is due to apoptotic cell death [5,[15][16][17][18][19][20]. To determine whether germ cells in regressing tubules of 23-mo-old rats were dying by apoptosis, we used an in situ method to identify apoptotic cells in serial sections of the testes that had been used to analyze CP-2/cathepsin L mRNA expression in normal, regressing, and regressed tubules.…”

Autophagy protects LNCaP cells under androgen deprivation conditions

“…Increased autophagosomes have been observed in the epithelial cells of the rat prostate gland after castration. 11,12 However, the specific relationship between autophagy and androgen is poorly known. In the study, we used LNCaP cells as an androgen-dependent prostate cancer cells model.…”

“…10 Previous studies have also reported that the number of autophagosomes was increased in the epithelial cells of rat prostate gland after castration. 11,12 Thus, it is probable that autophagy plays a role in prostate cancer cells when there is a lack of androgen.…”