LHRH antagonist cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia

Ferenc G. Rick, Andrew V Schally, Norman L Block, Gabor Halmos, Roberto Perez, Jesus B. Fernandez, Irving Vidaurre, Luca Szalontay

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)736-747
Number of pages12
JournalProstate
Volume71
Issue number7
DOIs
StatePublished - May 15 2011

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Prostatic Hyperplasia
Gonadotropin-Releasing Hormone
Prostate
Intercellular Signaling Peptides and Proteins
Cytokines
Gene Expression
LHRH Receptors
Real-Time Polymerase Chain Reaction
Weights and Measures
Interleukin-15
Injections
Corn Oil
Interleukin-13
Interleukin-17
Interleukin-3
Castration
Interleukin-5
Androgen Receptors
Fibroblast Growth Factor 2
Subcutaneous Injections

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 journalArticle

Rick, Ferenc G. ; Schally, Andrew V ; Block, Norman L ; Halmos, Gabor ; Perez, Roberto ; Fernandez, Jesus B. ; Vidaurre, Irving ; Szalontay, Luca. / LHRH antagonist cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia. In: Prostate. 2011 ; Vol. 71, No. 7. pp. 736-747.
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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.",
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AU - Schally, Andrew V

AU - Block, Norman L

AU - Halmos, Gabor

AU - Perez, Roberto

AU - Fernandez, Jesus B.

AU - Vidaurre, Irving

AU - Szalontay, Luca

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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.

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