scholarly journals The ElonginB/C-Cullin5-SOCS-Box-Complex Is a Potential Biomarker for Growth Hormone Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 201
Author(s):  
Wilhelm Gossing ◽  
Lars Radke ◽  
Henrik Biering ◽  
Sven Diederich ◽  
Knut Mai ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Deficiency ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Clinical Biomarkers ◽  
Potential Biomarker ◽  
Cullin 5 ◽  
Potential Benefits ◽  
Patient Groups ◽  
Socs Box

Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells’ sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism.

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

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 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

scholarly journals The SOCS box of suppressor of cytokine signaling-3 contributes to the control of G-CSF responsiveness in vivo

Blood ◽  
2007 ◽  
Vol 110 (5) ◽  
pp. 1466-1474 ◽  
Author(s):  
Kristy Boyle ◽  
Paul Egan ◽  
Steven Rakar ◽  
Tracy A. Willson ◽  
Ian P. Wicks ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Disease Model ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Mild Phenotype ◽  
Sh2 Domains ◽  
Inflammatory Stimuli ◽  
Socs Box

Abstract Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of granulocyte-colony stimulating factor (G-CSF) signaling in vivo. SOCS proteins regulate cytokine signaling by binding, via their SH2 domains, to activated cytokine receptors or their associated Janus kinases. In addition, they bind to the elongin B/C ubiquitin ligase complex via the SOCS box. To ascertain the contribution of the SOCS box of SOCS3 to in vivo regulation of G-CSF signaling, we generated mice expressing a truncated SOCS3 protein lacking the C-terminal SOCS box (SOCS3ΔSB/ΔSB). SOCS3ΔSB/ΔSB mice were viable, had normal steady-state hematopoiesis, and did not develop inflammatory disease. Despite the mild phenotype, STAT3 activation in response to G-CSF signaling was prolonged in SOCS3ΔSB/ΔSB bone marrow. SOCS3ΔSB/ΔSB bone marrow contained increased numbers of colony-forming cells responsive to G-CSF and IL-6. Treatment of the mice with pharmacologic doses of G-CSF, which mimics emergency granulopoiesis and therapeutic use of G-CSF, revealed that SOCS3ΔSB/ΔSB mice were hyperresponsive to G-CSF. Compared with wild-type mice, SOCS3ΔSB/ΔSB mice developed a more florid arthritis when tested using an acute disease model. Overall, the results establish a role for the SOCS box of SOCS3 in the in vivo regulation of G-CSF signaling and the response to inflammatory stimuli.

Sign in / Sign up

Export Citation Format

Share Document