Abstract
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 5α-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-γ, 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-β1, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 736-747 |
| Number of pages | 12 |
| Journal | Prostate |
| Volume | 71 |
| Issue number | 7 |
| DOIs | |
| State | Published - May 15 2011 |
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Keywords
- Benign prostatic hyperplasia
- Growth factors
- LHRH
- Proinflammatory cytokines
- Rats
ASJC Scopus subject areas
- Urology
- Oncology
Cite this
LHRH antagonist cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia. / Rick, Ferenc G.; Schally, Andrew V; Block, Norman L; Halmos, Gabor; Perez, Roberto; Fernandez, Jesus B.; Vidaurre, Irving; Szalontay, Luca.
In: Prostate, Vol. 71, No. 7, 15.05.2011, p. 736-747.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LHRH antagonist cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia
AU - Rick, Ferenc G.
AU - Schally, Andrew V
AU - Block, Norman L
AU - Halmos, Gabor
AU - Perez, Roberto
AU - Fernandez, Jesus B.
AU - Vidaurre, Irving
AU - Szalontay, Luca
PY - 2011/5/15
Y1 - 2011/5/15
N2 - 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 5α-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-γ, 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-β1, 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.
AB - 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 5α-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-γ, 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-β1, 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.
KW - Benign prostatic hyperplasia
KW - Growth factors
KW - LHRH
KW - Proinflammatory cytokines
KW - Rats
UR - http://www.scopus.com/inward/record.url?scp=79952774082&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952774082&partnerID=8YFLogxK
U2 - 10.1002/pros.21289
DO - 10.1002/pros.21289
M3 - Article
C2 - 20945403
AN - SCOPUS:79952774082
VL - 71
SP - 736
EP - 747
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 7
ER -