2005 Fiscal Year Final Research Report Summary
Regulatory mechanisms of blood flow in prostate gland
| Project/Area Number |
16591580
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Gunma University |
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Principal Investigator |
SHIBATA Yasuhiro GUNMA UNIVERSITY, SCHOOL OF MEDICINE, LECTURER, 医学部, 講師 (90344936)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Kazuhiro GUNMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 医学系研究科, 教授 (80312891)
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| Project Period (FY) |
2004 – 2005
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| Keywords | PROSTATE / BLOOD FLOW / HORMONE / VASCULAR ENDOTHELIAL GROWTH FACTOR / ADRENOMEDULLIN / PROSTAGLANDIN |
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| Research Abstract |
The prostate is a target organ of sex steroids and the regulation of prostate blood flow by sex hormones is currently under investigation. The suppressive effect of anti androgenic agents on prostate blood flow has already been put to practical use for the prevention of blood loss during prostate surgery. However the mechanism and signal transduction pathway of hormonal regulation of prostate blood flow has not yet been clarified. We studied the physiological effects of sex hormones on prostate blood flow and the factors involved in the signal transduction pathways using castrated rat model.
We examined the androgen that most effects prostate blood flow. Testosterone (T), dihydrotestosterone (DHT), dihydroepiandrostenedione (DHEA), T+finasteride or bovine serum albumin bound-testosterone (BSA-T) was administered to 2-day castrated rats. Prostate blood flow decreased rapidly from 12 hours castration to 36% of the normal level at 24 hours. The recruitment of prostate blood flow was observ
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ed in the T, DHT, T+finasteride and BSA-T administered groups, but not in the DHEA group. The strength of the effect on blood flow was strongest in the DHT treated group which suggested DHT as the major androgen regulating the prostate blood flow. The injection of cell membrane impermeable BSA-T showed a weaker but distinct blood flow recovery, that suggested the existence of transcription-independent non-genomic signal transduction pathway.
Based on the findings of several studies, we hypothesized that the vascular endothelial growth factor (VEGF) participate in the signaling pathway of prostate blood flow regulation. We examined the effect of VEGF on prostate blood flow and its participation in regulation of prostate blood flow by androgen. The decrease in prostate blood flow after castration was recovered to the normal level by the injection of VEGF or DHT. Co-administration of anti VEGF antibody with DHT completely abolished the androgen-induced increase in prostate blood flow. Up-regulations of VEGF-A mRNA expression were observed following androgen replacement in castrated rats. These results have clearly shown the involvement of VEGF in the signaling pathway of hormonal regulation of prostate blood flow.
We studied other factors such as adrenomedullin (ADM) and prostaglandin E2 (PGE2) that may be involved in the hormonal regulation of prostate blood flow. The results of the study clearly showed the direct regulation of prostate blood flow by ADM and PGE2 and its involvement in androgenic prostate blood flow regulation. Furthermore, ADM was estimated to be a downstream mediator of VEGF action in androgenic regulation of prostate blood flow.
In conclusion, blood flow regulation play an important role in hormonal regulation of prostate and various factors are involved in the signal transduction pathway. The development of treatments targeted toward those factors may be applicable to the treatment of prostate diseases. Less
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