期刊
PROSTATE
卷 71, 期 7, 页码 736-747出版社
WILEY-BLACKWELL
DOI: 10.1002/pros.21289
关键词
benign prostatic hyperplasia; LHRH; proinflammatory cytokines; growth factors; rats
资金
- Medical Research Service of the Veterans Affairs Department
- Department of Pathology and Medicine, Division of Hematology/Oncology of the Miller Medical School, University of Miami
- AEterna/Zentaris GmbH through South Florida Veterans Affairs Foundation for Research and Education
- L. Austin Weeks Endowment for Urologic Research
BACKGROUND. Recent findings suggest that BPH has an inflammatory component. Clinical trials have documented that therapy with LHRH antagonist Cetrorelix causes a marked and prolonged improvement in LUTS in men with symptomatic BPH. We investigated the mechanism of action and effect of Cetrorelix in a rat model of BPH. METHODS. Adult male Wistar rats were used. BPH was induced in rats by subcutaneous injections of TE 2 mg/day for 4 weeks. Control animals received injections of corn oil. After induction of BPH, rats received depot Cetrorelix pamoate at the doses of 0.625, 1.25, and 12.5 mg/kg on days 1 and 22 and TE-control rats received vehicle injections. Whole prostates were weighed and processed for RNA and protein. Real-time RT-PCR assays for numerous inflammatory cytokines and growth factors were performed. Quantitative analyses of prostatic LHRH receptor, LHRH, androgen receptor (AR) and 5 alpha-reductase 2 were done by real-time RT-PCR and immunoblotting; serum DHT, LH, PSA, and IGF-1 by immunoassays. RESULTS. mRNA levels for inflammatory cytokines IFN-gamma, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, IL-15, and IL-17 and for growth factors EGF, FGF-2, FGF-7, FGF-8, FGF-14, TGF-beta 1, and VEGF-A were significantly reduced by Cetrorelix 0.625 mg/kg (P < 0.05). Prostate weights were also significantly lowered by any dose of Cetrorelix. CONCLUSIONS. This study suggests that Cetrorelix reduces various inflammatory cytokines and growth factors in rat prostate and, at doses which do not induce castration levels of testosterone, can lower prostate weights. Our findings shed light on the mechanism of action of LHRH antagonists in BPH. Prostate 71: 736-747, 2011. (C) 2010 Wiley-Liss, Inc.
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