Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling

10.1038/nn954 ◽  
2002 ◽  
Vol 5 (11) ◽  
pp. 1155-1162 ◽  
Author(s):  
Ann M. Turnley ◽  
Clare H. Faux ◽  
Rodney L. Rietze ◽  
Jason R. Coonan ◽  
Perry F. Bartlett
Keyword(s):  
Growth Hormone ◽  
Neuronal Differentiation ◽  
Cytokine Signaling ◽  
Hormone Signaling ◽  
Suppressor Of Cytokine Signaling

scholarly journals Liver X receptor agonist downregulates growth hormone signaling in the liver

2011 ◽  
Vol 8 (2) ◽  
Author(s):  
Fahad Zadjali ◽  
Ruyman Santana-Farre ◽  
Mercedes Mirecki-Garrido ◽  
Ewa Ellis ◽  
Gunnar Norstedt ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hepatic Steatosis ◽  
Hepatic Metabolism ◽  
Liver X Receptor ◽  
Cytokine Signaling ◽  
Hormone Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Lxr Agonists ◽  
Liver X Receptor Agonist ◽  
Gh Receptors

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 (

scholarly journals CXCR4-mediated Suppressor of Cytokine Signaling Up-regulation Inactivates Growth Hormone Function

2004 ◽  
Vol 279 (43) ◽  
pp. 44460-44466 ◽  
Author(s):  
Ruth Garzón ◽  
Silvia F. Soriano ◽  
José Miguel Rodríguez-Frade ◽  
Lucio Gómez ◽  
Ana Martín de Ana ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling

Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3

2003 ◽  
Vol 284 (4) ◽  
pp. G646-G654 ◽  
Author(s):  
Lee A. Denson ◽  
Matthew A. Held ◽  
Ram K. Menon ◽  
Stuart J. Frank ◽  
Albert F. Parlow ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Inflammatory Diseases ◽  
Cytokine Signaling ◽  
Hormone Signaling ◽  
Tnf Receptor ◽  
Gh Receptor ◽  
Ghr Gene ◽  
Tnf Α ◽  
Socs Protein ◽  
Gh Resistance

Cytokines may cause an acquired growth hormone (GH) resistance in patients with inflammatory diseases. Anabolic effects of GH are mediated through activation of STAT5 transcription factors. We have reported that TNF-α suppresses hepatic GH receptor (GHR) gene expression, whereas the cytokine-inducible SH2-containing protein 1 (Cis)/suppressors of cytokine signaling ( Socs) genes are upregulated by TNF-α and IL-6 and inhibit GH activation of STAT5. However, the relative importance of these mechanisms in inflammatory GH resistance was not known. We hypothesized that IL-6 would prevent GH activation of STAT5 and that this would involve Cis/Socs protein upregulation. GH ± LPS was administered to TNF receptor 1 (TNFR1) or IL-6 null mice and wild-type (WT) controls. STAT5, STAT3, GHR, Socs 1–3, and Cis phosphorylation and abundance were assessed by using immunoblots, EMSA, and/or real time RT-PCR. TNF-α and IL-6 abundance were assessed by using ELISA. GH activated STAT5 in WT and TNFR1 or IL-6 null mice. LPS pretreatment prevented STAT5 activation in WT and TNFR1 null mice; however, STAT5 activation was preserved in IL-6 null mice. GHR abundance did not change with LPS administration. Inhibition of STAT5 activation by LPS was temporally associated with phosphorylation of STAT3 and upregulation of Cis and Socs-3 protein in WT and TNFR1 null mice; STAT3, Cis, and Socs-3 were not induced in IL-6 null mice. IL-6 inhibits hepatic GH signaling by upregulating Cis and Socs-3, which may involve activation of STAT3. Therapies that block IL-6 may enhance GH signaling in inflammatory diseases.

scholarly journals Distinct mechanisms of induction of hepatic growth hormone resistance by endogenous IL-6, TNF-α, and IL-1β

2014 ◽  
Vol 307 (2) ◽  
pp. E186-E198 ◽  
Author(s):  
Yueshui Zhao ◽  
Xiaoqiu Xiao ◽  
Stuart J. Frank ◽  
Herbert Y. Lin ◽  
Yin Xia
Keyword(s):  
Growth Hormone ◽  
Target Gene ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Gh Receptor ◽  
Tnf Α ◽  
Igf I ◽  
Socs3 Expression ◽  
Gh Resistance

During inflammation, the liver becomes resistant to growth hormone (GH) actions, leading to downregulation of the GH target gene IGF-I and activation of catabolism. Proinflammatory cytokines IL-6, TNF-α, and IL-1β are critically involved in the pathogenesis of hepatic GH resistance. However, the mechanisms used by endogenous IL-6, TNF-α, and IL-1β to inhibit the hepatic GH-IGF-I pathway during inflammation are not fully understood. Here, we show that TNF-α and IL-1β inhibited GH receptor (GHR) expression but had minor effects on the downstream suppressor of cytokine signaling (SOCS)3, while IL-6 induced SOCS3 expression but had no effect on GHR expression in Huh-7 cells. Consistent with the in vitro observations, neutralization of TNF-α and IL-1β in mouse models of inflammation did not significantly alter SOCS3 expression stimulated by inflammation but restored GHR and IGF-I expression suppressed by inflammation. Neutralization of IL-6 did not alter inflammation-suppressed GHR expression but drastically reduced the inflammation-stimulated SOCS3 expression and restored IGF-I expression. Interestingly, when the GH-IGF-I pathway was turned off by maximal inhibition of GHR expression, IL-6 and SOCS3 were no longer able to regulate IGF-I expression. Taken together, our results suggest that TNF-α/IL-1β and IL-6 use distinct mechanisms to induce hepatic GH resistance, with TNF-α and IL-1β acting primarily on GHR and IL-6 acting primarily on SOCS3. IL-6 action may be superseded by factors such as TNF-α and IL-1β that inhibit GHR expression.

scholarly journals Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction

FEBS Letters ◽  
1999 ◽  
Vol 453 (1-2) ◽  
pp. 63-66 ◽  
Author(s):  
Hélène Favre ◽  
Aurélie Benhamou ◽  
Joelle Finidori ◽  
Paul A. Kelly ◽  
Marc Edery
Keyword(s):  
Signal Transduction ◽  
Growth Hormone ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling
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