MP44-11 GROWTH HORMONE-RELEASING HORMONE (GHRH) ANTAGONISTS REDUCE INFLAMMATION- AND TRANSFORMING GROWTH FACTOR (TGF)-?2-INDUCED PROLIFERATION OF HUMAN BPH-1 PROSTATE EPITHELIAL CELLS GROWN IN 3D CULTURE

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2016MP44-11 GROWTH HORMONE-RELEASING HORMONE (GHRH) ANTAGONISTS REDUCE INFLAMMATION- AND TRANSFORMING GROWTH FACTOR (TGF)-?2-INDUCED PROLIFERATION OF HUMAN BPH-1 PROSTATE EPITHELIAL CELLS GROWN IN 3D CULTURE Petra Popovics, Andrew V. Schally, Roberto Perez, Rhenzi Cai, and Ferenc G. Rick Petra PopovicsPetra Popovics More articles by this author , Andrew V. SchallyAndrew V. Schally More articles by this author , Roberto PerezRoberto Perez More articles by this author , Rhenzi CaiRhenzi Cai More articles by this author , and Ferenc G. RickFerenc G. Rick More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.267AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benign prostatic hyperplasia (BPH) is frequently associated with chronic inflammation. Epithelial-to-mesenchymal transition (EMT) has been recently indicated as a major factor in the pathogenesis of BPH. Evidence also suggests that inflammatory cytokines may induce BPH. Hypothalamic neuropeptides, GHRH, luteinizing hormone-releasing hormone (LHRH) and their receptors are expressed in experimental models of BPH in which antagonists of GHRH and LHRH have been shown to suppress the levels of proinflammatory cytokines and alter the expression of genes related to EMT. These findings imply a role of GHRH/LHRH in the development of prostatitis, however, this has not been investigated to date. METHODS Human BPH-1 prostatic cell line was used to generate matrigel-embedded 3D cultures in which average sphere diameters were evaluated. Chronic inflammation was induced by treating cells with THP-1 macrophage-conditioned medium whereas EMT was triggered with TGF-ß1 or TGF-ß2 peptides. The role of secreted LHRH and GHRH in inflammation-induced proliferation was determined by using the LHRH antagonist, degarelix, and a specific GHRH antagonist developed in our lab. The presence of receptors for GHRH and LHRH was confirmed in 3D cultures by immunocytochemistry and quantitative RT-PCR. RESULTS BPH-1-derived spherical structures expressed cell membrane receptors for LHRH and GHRH. Macrophage-conditioned medium induced a 26% increase (P<0.001) in the average diameter of cells and a 2-fold elevation in the expression of the EMT markers N-cadherin (p<0.01) and Snail (p<0.001) as detected by qPCR. The expression of GHRH was also increased 2.7-fold (p<0.001), whereas mRNA levels of LHRH were slightly reduced (ns). GHRH antagonist reduced inflammation-induced increase in diameter by 64% (P<0.01), while no significant change was observed after degarelix treatment. TGF-ß2 increased average sphere diameter by 32%, but this effect was reduced by 67% by the GHRH antagonist (P<0.001). In contrast, TGF-ß1 did not significantly affect sphere diameter. CONCLUSIONS This study identifies GHRH as an important factor in inflammation-induced proliferation and TGF-ß2-triggered EMT of prostate epithelial cells and suggests the merit of further investigation to elucidate the effects of GHRH antagonists in the reduction of inflammation-induced BPH. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e602-e603 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Petra Popovics More articles by this author Andrew V. Schally More articles by this author Roberto Perez More articles by this author Rhenzi Cai More articles by this author Ferenc G. Rick More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...