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 red uced during the very early period after castration, and this reduction coin cides with the appearance of striking degenerative changes within the prost atic vascular system. These early effects on the prostate vascular system a re likely to be important for the subsequent regression of the ventral pros tate that occurs in response to castration. Since the endothelial cells of the ventral prostate do not express androgen receptor protein (AR), we prop osed that these early effects might be indirectly mediated by changes in th e local expression of vascular regulatory factors. In order to evaluate whe ther vascular endothelial growth factor-A (VEGF-A) might be among the prima ry mediators of these effects, we measured expression of VEGF-A mRNA and pr otein in the rat ventral prostate gland prior to and within the first 3 day s after castration. METHODS. Ventral prostate tissues were obtained from control (unoperated) r ats, sham-operated rats, or rats at sequential daily intervals (1-3 days) a fter 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 immunoh istochemistry, using an anti-VEGF-A antibody, was performed to localize VEG FA protein in the various cells of the tissue. Western blot analysis and a quantitative ELISA assay using anti-VEGF-A antibodies were performed to det ermine how VEGF-A protein expression in the rat ventral prostate was affect ed 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 character ized by a transient reduction of VEGFA mRNA expression (by approximately 50 %) on the second day after castration that was restored to higher than cont rol levels by the third day after castration. Immunohistochemical analysis for VEGF-A in control and castrated ventral prostates showed that the prost atic epithelial and smooth muscle cells were the major source of VEGF-A exp ression in this tissue. Quantitative analysis of VEGF-A protein expression by Western blot and ELISA methods confirmed a biphasic change in the expres sion of the polypeptide that correlated well with the results of the mRNA a nalyses. 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 change s in the ventral prostate vascular system are already evident by 1 day afte r castration, we believe that these findings indicate that VEGF-A is not li kely 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.