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Direct Regulation of Prostate Blood Flow by Vascular Endothelial Growth Factor and Its Participation in the Androgenic Regulation of Prostate Blood Flow in Vivo

Department of Urology (Y.S., B.K., S.A., Y.F., K.S., H.Y.), Graduate School of Medicine, Gunma University, Maebashi 371-8511; and Department of Pharmacological Research (S.H.), Teikoku Hormone Manufacturing, Kawasaki 213-0033, Japan

Address all correspondence and requests for reprints to: Yasuhiro Shibata, Department of Urology, Graduate School of Medicine, Gunma University, 3-39 Showa-machi, Maebashi, Gunma 371-8511, Japan. E-mail: yshibata{at}med.gunma-u.ac.jp.

Previous studies on prostate blood flow regulation have indicated that androgen regulates prostate blood flow. However, the mechanism responsible for this regulation is unknown. In the present study, we focused on the effects of vascular endothelial growth factor (VEGF), a key factor responsible for angiogenesis and androgenic blood flow regulation. We examined in vivo the effect of VEGF on prostate blood flow and its participation in the androgenic regulation of this blood flow using a castrated rat model following subcapsular intraprostatic injection method. We found that VEGF is involved in blood flow regulation with an activity equal to that of dihydrotestosterone (DHT). The effect of VEGF on prostate blood flow was already seen at 30 min after the administration. The elevating effect of DHT on castrated rat prostate blood flow was abolished by coadministration of DHT with neutralizing anti-VEGF antibody. The change in VEGF-A mRNA expression in response to androgen stimulation was examined by double-fluorescent probe quantitative PCR (Taqman PCR). The results showed that androgenic regulation of VEGF gene expression occurred shortly after androgen stimulation. VEGF gene up-regulation was abolished or down-regulated by coadministration of neutralizing anti-VEGF antibody. This is the first report on the importance of VEGF in the androgenic regulation signaling pathway that affects prostate blood flow. Alternative treatment targeted toward anti-VEGF activity as a substitute for ordinary antiandrogenic therapy may be effective against prostate diseases, especially those with androgen-independent and hyperhemorrhagic status.

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