Remodeling of rat ventral prostate after castration involves heparanase-1

Abstract

Androgen deprivation causes the rat ventral prostate to reduce to 10% of its original size by 21 days after castration. The regressive changes result from the loss of epithelial cells by apoptosis and marked reorganization of the stroma. We have investigated whether these changes are accompanied by variations in heparanase expression. The ventral prostate of castrated rats was collected and processed for the quantification of heparan sulfate (HS), for the measurement of heparanase expression and its localization by reverse transcription/polymerase chain reaction, Western blotting, and immunohistochemistry, and for transmission electron microscopy (TEM). Absolute HS content decreased significantly as early as day 7 after surgery. Heparanase mRNA peaked 7 days after castration. The heparanase proenzyme (65 kDa) and the active form (50 kDa) were identified and peaked on day 7 after castration; this coincided with maximum HS-degrading activity. Heparanase was located to the basolateral surface of epithelial cells and in the adjacent stroma. After castration, staining for heparanase was reduced in the epithelium and increased in the stroma. TEM revealed that the peak of heparanase expression at day 7 after castration was associated with extensive changes in the basement membrane of the epithelium, endothelium and smooth muscle cells involving cell shrinkage and/or deletion by apoptosis. These results suggest that heparanase expression increases after castration and correlates with a decreased amount of HS. This variation in heparanase expression is involved in tissue remodeling and in the control of the regressive pattern after 1 week of androgen deprivation.

Effect of Prolactin on the Population of Epithelial Cells From Ventral Prostate of Intact and Cyproterone Acetate‐Treated Peripubertal Rats: Stereological and Immunohistochemical Study

“…As we have focused our study on the epithelium, the epithelial regressive changes observed (i.e., a decrease in the amount of epithelial cells) could be either due to a low rate of cell proliferation, an increase of the apoptosis, or both. The androgenic blockade causes a decrease in the global size of the peripubertal ventral prostate, according to that described by other authors, which concern the regressive changes shown in the prostate after androgenic deprivation in both adult and prepubertal rats (Vilamaior et al, 2006;Pereira et al, 2006;Augusto et al, 2008). Controversy exists regarding the influence of PL on the prostate of pharmacologically castrated rats (either immature or mature).…”

“…Although the rat prostate is an androgen-dependent organ, several studies indicate that it is androgen-sensitive, but does not require a chronic androgenic stimulus (Donjacour and Cunha, 1988). This androgen-dependence was demonstrated by the dramatic changes observed in rat prostate after surgical or pharmacological castration: androgenic deprivation causes regressive alterations due to the decrease of epithelial cells by apoptosis and to stromal reorganization (Potter et al, 2006;Augusto et al, 2008). In this sense, cyproterone acetate (CA), currently employed in antiandrogenic therapy for prostate cancer, is a potent and specific antagonist of steroid androgens in competition with dihydrotestosterone in the binding of androgen receptors (AR).…”

Neonatal exposure to high doses of 17β-estradiol results in inhibition of heparanase-1 expression in the adult prostate

“…2). This *50 kDa band correspond to the active form of HPSE-1 previously identified in the VP (Augusto et al 2008), and established the specificity of the antibody. Densitometric analysis of the bands, considering total actin as internal control revealed a 33% reduction in HPSE-1 content in the VP of estogenized animals.…”

“…Its activity was associated with cellcell and cell-ECM interactions, and was first described in tumor progression. It is well known that tumor prostate cells and also normal rat prostate cells express HPSE-1 (Kosir et al 1997;Augusto et al 2008).…”

“…Recently, we demonstrated that the expression of HPSE-1 was transiently increased after castration, showing a transition from epithelial to stromal cells (Augusto et al 2008).…”