{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:01:57Z","timestamp":1787770917288,"version":"build-2784847793"},"reference-count":61,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T00:00:00Z","timestamp":1526860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006280","name":"Urology Care Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006280","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammation plays a key role in the etiology of benign prostatic hyperplasia (BPH) through multiple pathways involving the stimulation of proliferation by cytokines and growth factors as well as the induction of the focal occurrence of epithelial\u2010to\u2010mesenchymal transition (EMT). We have previously reported that GHRH acts as a prostatic growth factor in experimental BPH and in autoimmune prostatitis models and its blockade with GHRH antagonists offer therapeutic approaches for these conditions. Our current study was aimed at the investigation of the beneficial effects of GHRH antagonists in \u03bb\u2010carrageenan\u2010induced chronic prostatitis and at probing the downstream molecular pathways that are implicated in GHRH signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To demonstrate the complications triggered by recurrent\/chronic prostatic inflammation in Sprague\u2010Dawley rats, 50\u2009\u03bcL 3% carrageenan was injected into both ventral prostate lobes two times, 3 weeks apart. GHRH antagonist, MIA\u2010690, was administered 5 days after the second intraprostatic injection at 20\u2009\u03bcg daily dose for 4 weeks. GHRH\u2010induced signaling events were identified in BPH\u20101 and in primary prostate epithelial (PrEp) cells at 5, 15, 30, and 60\u2009min with Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inflammation induced prostatic enlargement and increased the area of the stromal compartment whereas treatment with the GHRH antagonist significantly reduced these effects. This beneficial activity was consistent with a decrease in prostatic GHRH, inflammatory marker COX\u20102, growth factor IGF\u20101 and inflammatory and EMT marker TGF\u2010\u03b21 protein levels and the expression of multiple genes related to EMT. In vitro, GHRH stimulated multiple pathways involved in inflammation and growth in both BPH\u20101 and PrEp cells including NF\u03baB p65, AKT, ERK1\/2, EGFR, STAT3 and increased the levels of TGF\u2010\u03b21 and Snail\/Slug. Most interestingly, GHRH also stimulated the transactivation of the IGF receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The study demonstrates that GHRH antagonists could be beneficial for the treatment of prostatic inflammation and BPH in part by inhibiting the growth\u2010promoting and inflammatory effects of locally produced GHRH.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23655","type":"journal-article","created":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T03:27:33Z","timestamp":1526959653000},"page":"970-980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Growth hormone\u2010releasing hormone antagonists reduce prostatic enlargement and inflammation in carrageenan\u2010induced chronic prostatitis"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9179-0575","authenticated-orcid":false,"given":"Petra","family":"Popovics","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Miller School of Medicine University of Miami Miami Florida"},{"name":"Endocrine, Polypeptide and Cancer Institute Veterans Affairs Medical Center Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhi","family":"Cai","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Miller School of Medicine University of Miami Miami Florida"},{"name":"Endocrine, Polypeptide and Cancer Institute Veterans Affairs Medical Center Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sha","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Miller School of Medicine University of Miami Miami Florida"},{"name":"Endocrine, Polypeptide and Cancer Institute Veterans Affairs Medical Center Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc G.","family":"Rick","sequence":"additional","affiliation":[{"name":"Endocrine, Polypeptide and Cancer Institute Veterans Affairs Medical Center Miami Florida"},{"name":"Department of Urology, Herbert Wertheim College of Medicine Florida International, University Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-6747","authenticated-orcid":false,"given":"Andrew V.","family":"Schally","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Miller School of Medicine University of Miami Miami Florida"},{"name":"Endocrine, Polypeptide and Cancer Institute Veterans Affairs Medical Center Miami Florida"},{"name":"Sylvester Comprehensive Cancer Center, Department of Medicine, Miller School of Medicine University of Miami Miami Florida"},{"name":"Division of Hematology\/Oncology, Department of Medicine Miller School of Medicine University of Miami Miami Florida"},{"name":"Department of Pathology, Miller School of Medicine University of Miami Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,21]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"S3","article-title":"Benign prostatic hyperplasia: an overview","volume":"7","author":"Roehrborn CG","year":"2005","journal-title":"Rev Urol"},{"key":"e_1_2_8_3_1","first-page":"340","article-title":"Origin and evolution of benign prostatic enlargement","volume":"15","author":"McNeal JE","year":"1978","journal-title":"Invest Urol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2006.05.001"},{"key":"e_1_2_8_5_1","first-page":"1","article-title":"Benign prostatic hyperplasia: epidemiology, economics and evaluation","volume":"22","author":"Vuichoud C","year":"2015","journal-title":"Can J Urol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.01.074"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2012.658040"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01299-7"},{"key":"e_1_2_8_9_1","first-page":"51","article-title":"Persistent sexual dysfunction and depression in finasteride users for male pattern hair loss: a serious concern or red herring","volume":"7","author":"Singh MK","year":"2014","journal-title":"J Clin Aesthet Dermatol"},{"key":"e_1_2_8_10_1","first-page":"S14","article-title":"Side Effects of alpha\u2010Blocker use: retrograde ejaculation","volume":"11","author":"Kaplan SA","year":"2009","journal-title":"Rev Urol"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1557988313510732"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-015-0099-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2004.10.017"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2004.12.008"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(20000101)42:1<45::AID-PROS6>3.0.CO;2-W"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500221"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12118"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)56980-3"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.355164"},{"key":"e_1_2_8_20_1","first-page":"939","article-title":"The androgen receptor plays different roles in macrophage\u2010induced proliferation in prostate stromal cells between transitional and peripheral zones of benign prostatic hypertrophy","volume":"16","author":"Xu D","year":"2017","journal-title":"EXCLI J"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2012-1079"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620884114"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21071"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.05.012"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22814"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.2.511"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2011.03.006"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120588109"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20001001)45:2<158::AID-PROS10>3.0.CO;2-K"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0677"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323102111"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2017.01.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018086108"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2011.11.081"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22633"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.25.12298"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096824"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000338"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801875"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23043"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0159490"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500930"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.17221\/6758-VETMED"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00380.2006"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708833200"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8634865"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22580"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20984"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22773"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618582114"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012101031"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.06.007"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.02.011"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-014-0131-4"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2016.11.004"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02631333"},{"key":"e_1_2_8_57_1","first-page":"117","article-title":"Effect of acute and chronic inflammation on plasma growth hormone levels in rats","volume":"23","author":"Corsi MM","year":"1997","journal-title":"Drugs Exp Clin Res"},{"key":"e_1_2_8_58_1","first-page":"3825","article-title":"Insulin\u2010like growth factor (IGF)\u2010I, IGF\u2010II and IGF type I receptor (IGFR\u2010I) expression in prostatic cancer","volume":"23","author":"Cardillo MR","year":"2003","journal-title":"Anticancer Res"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.192534"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00029.2013"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2460"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1316447111"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.23655","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.23655","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T08:24:15Z","timestamp":1695025455000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.23655"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,21]]},"references-count":61,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/pros.23655"],"URL":"https:\/\/doi.org\/10.1002\/pros.23655","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,21]]},"assertion":[{"value":"2018-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}