title: Participation of adrenomedullin and its relation with vascular endothelial growth factor in androgen regulation of prostatic blood flow in vivo.
abstract: OBJECTIVE
  We had previously reported that androgen-regulated prostatic blood flow and vascular endothelial growth factor (VEGF) were involved in the signal transduction pathway. Adrenomedullin (ADM) is a multifunctional regulatory peptide with mitogenic and angiogenic capabilities that are regulated by androgen. ADM is abundantly expressed in the prostate. We focused on ADM and evaluated its participation and relation with VEGF in androgen prostatic blood flow regulation using a castrated rat model.
  
  
  METHODS
  We examined the effect of locally injected dihydrotestosterone (DHT) and ADM, and the co-administration of DHT with an ADM receptor antagonist (ADM 22-52) on prostatic blood flow. Furthermore, prostatic blood flow was evaluated after ADM and VEGF administration with each other's antagonist, VEGF neutralizing antibody and ADM 22-52, respectively. Changes in the mRNA expression levels of ADM in the prostate after castration and successive androgen stimulation were also evaluated.
  
  
  RESULTS
  The administration of ADM promptly increased prostatic blood flow in a dose-dependent manner within 30 minutes. The DHT-induced increase in prostatic blood flow was completely abolished by co-administration with anti-ADM. Anti-ADM inhibited the VEGF-induced prostatic blood flow elevation, but a VEGF neutralizing antibody did not affect the ADM-mediated blood flow elevation. Furthermore, upregulation of the ADM gene induced by DHT was inhibited by co-administration with a VEGF-neutralizing antibody.
  
  
  CONCLUSIONS
  These results have clearly demonstrated the direct regulation of prostatic blood flow by ADM and its involvement in androgenic prostatic blood flow regulation. Furthermore, ADM was estimated to be a downstream mediator of VEGF action in the signal transduction pathway.
authors.affiliation: Department of Urology, Gunma University Graduate School of Medicine, Gunma, Japan. yshibata@med.gunma-u.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Bunzo
authors.initials: B
authors.lastname: Kashiwagi
authors.forename: Seiji
authors.initials: S
authors.lastname: Arai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Magari
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Seijiro
authors.initials: S
authors.lastname: Honma
mesh_terms: D053607:Adrenomedullin / Q000502:physiology*; D000728:Androgens / Q000502:physiology*; D000818:Animals; D008297:Male; D011467:Prostate / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D000728:Androgens; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin