Document Detail


Participation of adrenomedullin and its relation with vascular endothelial growth factor in androgen regulation of prostatic blood flow in vivo.
MedLine Citation:
PMID:  17113911     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: 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:
Yasuhiro Shibata; Bunzo Kashiwagi; Seiji Arai; Tomohiro Magari; Kazuhiro Suzuki; Seijiro Honma
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Urology     Volume:  68     ISSN:  1527-9995     ISO Abbreviation:  Urology     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-20     Completed Date:  2006-12-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366151     Medline TA:  Urology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1127-31     Citation Subset:  IM    
Affiliation:
Department of Urology, Gunma University Graduate School of Medicine, Gunma, Japan. yshibata@med.gunma-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adrenomedullin / physiology*
Androgens / physiology*
Animals
Male
Prostate / blood supply*
Rats
Rats, Wistar
Regional Blood Flow / physiology
Vascular Endothelial Growth Factor A / physiology*
Chemical
Reg. No./Substance:
0/Androgens; 0/Vascular Endothelial Growth Factor A; 148498-78-6/Adrenomedullin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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