Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/54696
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dc.contributor.authorZadjali, Fahaden_US
dc.contributor.authorFlores-Morales, Amilcaren_US
dc.contributor.authorNorstedt, Gunnaren_US
dc.contributor.authorSantana-Farre, Ruymanen_US
dc.contributor.authorMirecki-Garrido, Mercedesen_US
dc.contributor.authorEllis, Ewaen_US
dc.contributor.authorFernandez-Perez, Leandroen_US
dc.date.accessioned2019-02-18T12:34:54Z-
dc.date.available2019-02-18T12:34:54Z-
dc.date.issued2011en_US
dc.identifier.issn1868-1883en_US
dc.identifier.otherWoS-
dc.identifier.urihttp://hdl.handle.net/10553/54696-
dc.description.abstractLiver X receptor (LXR) agonists have been shown to influence the development of hyperlipidemia and atherosclerosis in mouse models. It has also been demonstrated that some LXR agonists can cause hepatic steatosis in experimental animals. Growth hormone (GH) is known to regulate hepatic metabolism and the absence of hepatic GH receptors (GHR) leads to hepatic steatosis. In this study., we analyzed whether the actions of LXR agonists could involve interference with GH signaling. We showed that LXR agonists impair GH signaling in hepatocytes. LXR agonist treatment attenuated GH induction of suppressor of cytokine signaling 2 (SOCS2), SOCS3, and CIS mRNA levels in BRL-4 cells. Likewise., the activity of a luciferase reporter vector driven by the GH response element (GHRE) of the SOCS2 gene was inhibited by simultaneous treatment with an LXR agonist. The inhibitory effect of LXR agonists on GH signals can be mimicked by overexpres-sion of the LXR regulated factors., sterol regulatory element binding protein 1 (SREBP1) and SREBP2, in hepatic cells. In both cases total and phosphorylated signal transducers and activators of transcription 5b (STAT5b) protein levels were significantly reduced. DNA binding assays demonstrated that SREBP1 binds to an E-box within a previously defined GHRE in the SOCS2 gene promoter., but does not compete with STAT5b binding to a nearby site in the same promoter construct. Taken together., our findings indicate that the inhibitory effects of LXR agonists on GH signaling are mediated by SREBP1, through the downregulation of STAT5b gene transcription and stimulation of STAT5b protein degradation. The findings provide a new insight into the understanding of the molecular actions of LXR agonists., which may be of relevance to their pharmacological actions. © 2011, by Walter de Gruyter Berlin Boston. All rights reserved.en_US
dc.languagespaen_US
dc.publisher1868-1883-
dc.relation.ispartofHormone Molecular Biology and Clinical Investigationen_US
dc.sourceHormone Molecular Biology and Clinical Investigation[ISSN 1868-1883],v. 8, p. 471-478en_US
dc.subject.otherGene-Expressionen_US
dc.subject.otherLipogenesisen_US
dc.subject.otherActivationen_US
dc.subject.otherSuppressoren_US
dc.subject.otherInsulinen_US
dc.subject.otherGlucoseen_US
dc.subject.otherStat5Aen_US
dc.subject.other9-Cis Retinoic Aciden_US
dc.subject.otherGrowth Hormoneen_US
dc.subject.otherLipiden_US
dc.subject.otherLxren_US
dc.subject.otherRxren_US
dc.subject.otherSocs2en_US
dc.subject.otherT0901317en_US
dc.titleLiver X receptor agonist downregulates growth hormone signaling in the liveren_US
dc.typeinfo:eu-repo/semantics/Articleen_US
dc.typeArticleen_US
dc.identifier.doi10.1515/HMBCI.2011.125en_US
dc.identifier.scopus84891731025-
dc.identifier.isi000214511600002-
dc.contributor.authorscopusid23011004900-
dc.contributor.authorscopusid57203543358-
dc.contributor.authorscopusid57203543352-
dc.contributor.authorscopusid57200400684-
dc.contributor.authorscopusid7006397634-
dc.contributor.authorscopusid15830358800-
dc.contributor.authorscopusid57200400684-
dc.contributor.authorscopusid15830358800-
dc.contributor.authorscopusid55221793700-
dc.contributor.authorscopusid12788528200-
dc.contributor.authorscopusid55221793700-
dc.contributor.authorscopusid12788528200-
dc.contributor.authorscopusid57200400684-
dc.identifier.eissn1868-1891-
dc.description.lastpage478en_US
dc.identifier.issue2-
dc.description.firstpage471en_US
dc.relation.volume8en_US
dc.investigacionCiencias de la Saluden_US
dc.type2Artículoen_US
dc.contributor.daisngid1793904-
dc.contributor.daisngid3808417-
dc.contributor.daisngid4588303-
dc.contributor.daisngid289908-
dc.contributor.daisngid178539-
dc.contributor.daisngid795544-
dc.contributor.daisngid617657-
dc.description.numberofpages8en_US
dc.utils.revisionen_US
dc.contributor.wosstandardWOS:Zadjali, F-
dc.contributor.wosstandardWOS:Santana-Farre, R-
dc.contributor.wosstandardWOS:Mirecki-Garrido, M-
dc.contributor.wosstandardWOS:Ellis, E-
dc.contributor.wosstandardWOS:Norstedt, G-
dc.contributor.wosstandardWOS:Fernandez-Perez, L-
dc.contributor.wosstandardWOS:Flores-Morales, A-
dc.date.coverdateEnero 2011en_US
dc.identifier.ulpgces
dc.description.esciESCI
item.fulltextCon texto completo-
item.grantfulltextopen-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Ciencias Clínicas-
crisitem.author.orcid0000-0002-0828-8921-
crisitem.author.orcid0000-0001-7802-465X-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameFlores Morales,Amilcar-
crisitem.author.fullNameFernández Pérez, Leandro Francisco-
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