Vascular endothelial growth factor-A expression in the rat ventral prostate gland and the early effects of castration

BACKGROUND. Blood flow to the rat ventral prostate gland is drastically reduced during the very early period after castration, and this reduction coincides with the appearance of striking degenerative changes within the prostatic vascular system. These early effects on the prostate vascular system are likely to be important for the subsequent regression of the ventral prostate that occurs in response to castration. Since the endothelial cells of the ventral prostate do not express androgen receptor protein (AR), we proposed that these early effects might be indirectly mediated by changes in the local expression of vascular regulatory factors. In order to evaluate whether vascular endothelial growth factor-A (VEGF-A) might be among the primary mediators of these effects, we measured expression of VEGF-A mRNA and protein in the rat ventral prostate gland prior to and within the first 3 days after castration. METHODS. Ventral prostate tissues were obtained from control (unoperated) rats, sham-operated rats, or rats at sequential daily intervals (1-3 days) after castration. A quantitative RNase protection assay and a comparative RT-PCR assay were used to evaluate the extent to which the expression of VEGF-A mRNA in the ventral prostate was affected by castration. In situ immunohistochemistry, using an anti-VEGF-A antibody, was performed to localize VEGFA protein in the various cells of the tissue. Western blot analysis and a quantitative ELISA assay using anti-VEGF-A antibodies were performed to determine how VEGF-A protein expression in the rat ventral prostate was affected by castration. RESULTS. Results of VEGF-A mRNA analysis in the rat ventral prostate gland during the first 3 days after castration showed a biphasic change characterized by a transient reduction of VEGFA mRNA expression (by approximately 50%) on the second day after castration that was restored to higher than control levels by the third day after castration. Immunohistochemical analysis for VEGF-A in control and castrated ventral prostates showed that the prostatic epithelial and smooth muscle cells were the major source of VEGF-A expression in this tissue. Quantitative analysis of VEGF-A protein expression by Western blot and ELISA methods confirmed a biphasic change in the expression of the polypeptide that correlated well with the results of the mRNA analyses. CONCLUSIONS. VEGF-A expression in the ventral prostate gland of the Sprague-Dawley rat is downregulated on the second day after castration but returns to control levels by the third day after castration. Since critical changes in the ventral prostate vascular system are already evident by 1 day after castration, we believe that these findings indicate that VEGF-A is not likely to be the critical or sole mediator of the early effects of castration on the vascular system of the rat ventral prostate gland. Prostate 43:184-194, 2000. (C) 2000 Wiley-Liss, Inc.