Effect of Castration on Extracellular Matrix Remodeling and Angiogenesis of the Prostate Gland

Abstract

Abstract. This study was conducted to evaluate the long term effect of castration on the prostate gland proliferation, extracellular matrix remodeling and angiogenesis. Prostate gland proliferation was assessed by immunolocalization of proliferating cell nuclear antigen (PCNA). The expression level of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and metaloprotenase-13 (MMP-13) by the prostate gland were assessed by immunohistochemistry and quantitative real-time PCR. The expression of the above mentioned parameters by the prostate gland of mature intact dogs were compared to that of castrated dogs six months post-castration. The results showed that castration induced a remarkable atrophy of the prostate gland which was associated with a highly significant decrease in the PCNA proliferation index. Although TGF-β protein was immunolocalized to the epithelial and stroma cells of the prostate gland from both intact and castrated dogs, castration induced a significant up-regulation of TGF-β mRNA expression. VEGF mRNA expression and its encoded protein immunolocalization were decreased significantly by the prostate gland from castrated dogs as compared to that of intact dogs. Castration, on the other hand, resulted in no significant change in MMP-13 mRNA expression despite an effect on its cellular immunolocalization which appeared to be localized to the epithelial and stromal cells of the prostate gland from castrated dogs as compared to epithelial cells of the prostate gland from intact dogs. These results indicated that castration-induced prostate gland regression continued to exert a potent suppressive effect on prostate gland proliferation which might be mediated by the elevated level of TGF-β. Moreover, the low expression level of VEGF might reflect a reduced blood flow demand by the regressed and growthdormant prostate after castration.

ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment

“…5C). Despite significant atrophy and the well-described increase in prostatic apoptosis following castration (15), there was no change in apoptotic-rate in ARN-509-treated prostates (TUNEL-staining), suggesting that atrophy, if driven by apoptosis, was advanced and complete at 28 days of treatment (Fig. 5C).…”

Yaşlı Farelerin Beyninde Testosteron Takviyesinin Anjiyogenik Etkisi

“…In vivo, a transient increase in the weight of ventral lobes of the prostate gland and 7-fold increase in specific activity of VEGF belong to prostate in testosterone injected rats were seen. After castration a decrease is observed in both translation and transcription levels of VEGF of the prostate gland of the dog [6] . Also in cancer cells culture, an increase of transcription of VEGF is found after estrogens and androgens treatment [16] .…”

“…Few studies have been made regarding the effects of androgens on angiogenesis [6,7] . It was determined that androgens stimulate erythropoietin production via VEGF in cell culture and endothelial stem cells are regulated hormonally.…”

“…For RNA extraction and PCR procedures of standardization and control the housekeeping transcript (GAPDH) was used. Genes were amplified using QuantiTect SYBR PCR Kit (ABM) as defined by Shidaifat et al [6] .…”

“…by expression and releasing of angiogenic factors in female [3][4][5] . There are few and limited studies about the effect of testosterone on angiogenesis [6,7] . In addition to the factors mentioned above angiogenesis are also affected by the age.…”