MP17-03 INFLAMMATION-INDUCED PROSTATIC ENLARGEMENT AND PROLIFERATION OF PROSTATE EPITHELIAL CELLS IS REDUCED BY GROWTH HORMONE-RELEASING HORMONE (GHRH) ANTAGONISTS THROUGH THE INHIBITION OF EPITHELIAL-TO-MESENCHYMAL TRANSITION

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2017MP17-03 INFLAMMATION-INDUCED PROSTATIC ENLARGEMENT AND PROLIFERATION OF PROSTATE EPITHELIAL CELLS IS REDUCED BY GROWTH HORMONE-RELEASING HORMONE (GHRH) ANTAGONISTS THROUGH THE INHIBITION OF EPITHELIAL-TO-MESENCHYMAL TRANSITION Petra Popovics, Andrew Schally, Luis Salgueiro, Krisztina Kovacs, and Ferenc Rick Petra PopovicsPetra Popovics More articles by this author , Andrew SchallyAndrew Schally More articles by this author , Luis SalgueiroLuis Salgueiro More articles by this author , Krisztina KovacsKrisztina Kovacs More articles by this author , and Ferenc RickFerenc Rick More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.592AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The pathogenesis of benign prostatic hyperplasia (BPH) has been associated with various factors including hormonal imbalance, inflammation-induced cell proliferation and epithelial-to-mesenchymal transition. We have previously demonstrated that prostatic GHRH and its receptors are upregulated in a rat testosterone-induced BPH model and GHRH antagonists suppress the levels of proinflammatory cytokines. Based on these findings, we investigated the role of GHRH in inflammation-induced proliferation of prostate epithelial cells in vitro and prostate enlargement in experimental autoimmune prostatitis. METHODS Autoimmune inflammation in the prostates of Balb/c mice was induced by subcutaneous injections of rat male tissue homogenate. Changes in prostate volume were measured with the VEVO® 1100 ultrasound imaging system. Human BPH-1 and primary prostate epithelial cells were used in matrigel-embedded 3D cultures and average sphere diameters were evaluated. Chronic inflammation was mimicked by treating cells with THP-1 macrophage-conditioned medium or Il-17A, whereas EMT was triggered with TGF-β1 or TGF-β2 peptides. The role of secreted GHRH in inflammation-induced proliferation was determined by using GHRH antagonists developed in our lab. Changes in the protein levels were determined by western blot. RESULTS Experimental autoimmune prostatitis increased the volume of the ventral prostate by 92% at week 8 compared to control (p<0.001). A 1-month daily treatment with GHRH antagonists caused a significant, 48% reduction in prostate volume. Macrophage-conditioned medium induced a 26% increase (p<0.001) in the average diameter of cells and elevation in the expression of mesenchymal markers. The mRNA and protein expression of GHRH were significantly increased by macrophage-conditioned medium. GHRH antagonist reduced inflammation- and TGF-β2-induced increase in diameter by 64% (p<0.01) and by 67% (p<0.001), respectively, and reduced the expression of n-cadherin. The stimulatory effect of TGF-β2 was abolished when GHRH receptor expression was silenced by stable transfection of shRNA. IL-17A stimulation of the growth of primary epithelial cells were also significantly reduced by GHRH antagonists. CONCLUSIONS Our results indicate that GHRH is a key factor in prostatic inflammation-induced prostate enlargement and EMT and suggest that GHRH antagonists have beneficial effects in chronic prostatitis and BPH. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e212 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Petra Popovics More articles by this author Andrew Schally More articles by this author Luis Salgueiro More articles by this author Krisztina Kovacs More articles by this author Ferenc Rick More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...