Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/54696
Title: Liver X receptor agonist downregulates growth hormone signaling in the liver
Authors: Zadjali, Fahad
Flores-Morales, Amilcar 
Norstedt, Gunnar
Santana-Farre, Ruyman
Mirecki-Garrido, Mercedes
Ellis, Ewa
Fernandez-Perez, Leandro 
Keywords: Gene-Expression
Lipogenesis
Activation
Suppressor
Insulin, et al
Issue Date: 2011
Publisher: 1868-1883
Journal: Hormone Molecular Biology and Clinical Investigation 
Abstract: Liver 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.
URI: http://hdl.handle.net/10553/54696
ISSN: 1868-1883
DOI: 10.1515/HMBCI.2011.125
Source: Hormone Molecular Biology and Clinical Investigation[ISSN 1868-1883],v. 8, p. 471-478
Appears in Collections:Artículos
Thumbnail
Liver_X
Adobe PDF (656,03 kB)
Show full item record

SCOPUSTM   
Citations

3
checked on May 9, 2021

WEB OF SCIENCETM
Citations

3
checked on May 9, 2021

Page view(s)

32
checked on May 15, 2021

Download(s)

41
checked on May 15, 2021

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.