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Cis desensitizes GH induced Stat5 signaling in rat liver cells
H Karlsson1, J A Gustafsson, A Mode
1Department of Medical Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden. hanna.karlsson@mednut.ki.se
Abstract:
Recently a novel family of proteins, the Cis/Socs family, has been shown to constitute negative regulators of cytokine-induced Jak/Stat signaling. Here we demonstrate that Socs-2 and Cis mRNA expression in rat liver is dependent on the presence of growth hormone (GH), and that GH induce Cis mRNA expression in cultures of primary rat hepatocytes. Furthermore, cotransfection studies in the rat liver cell line, BRL-4, revealed that constitutive expression of Cis, but not Socs-2, inhibited the GH-induced transactivation of a Stat5-responsive reporter gene construct. This indicates a functional role for Cis in the desensitization of GH activated Jak/Stat5 signaling in rat liver cells. In response to the intermittent pattern of GH secretion in male rats, GH activates Stat5b signaling whereas this activation is blunted in female rats having a continuous pattern of GH secretion. We hypothesize that GH induction of Cis could be one mechanism by which sexually dimorphic GH signaling via Stat5b is achieved in the rat liver.
Insights
Growth hormone (GH) induces Cis mRNA in rat liver cells, a key step in regulating Jak/Stat signaling. Cis protein plays a role in the sexually dimorphic GH signaling observed in rats.
Area of Science:
- Molecular Biology
- Endocrinology
- Cell Signaling
Background:
- The Cis/Socs protein family acts as negative regulators of cytokine-induced Janus kinase/Signal transducer and activator of transcription (Jak/Stat) signaling pathways.
- Growth hormone (GH) signaling is crucial in various physiological processes and exhibits sex-specific patterns in rats.
Purpose of the Study:
- To investigate the role of Cis and Socs-2 proteins in growth hormone (GH)-mediated Jak/Stat signaling in rat liver.
- To explore the potential involvement of Cis in the sexually dimorphic regulation of GH signaling.
Main Methods:
- Quantitative analysis of Socs-2 and Cis mRNA expression in rat liver under GH influence.
- In vitro studies using primary rat hepatocytes to assess GH-induced Cis mRNA expression.
- Cotransfection experiments in the BRL-4 rat liver cell line to evaluate the functional impact of Cis and Socs-2 on GH-activated Stat5 signaling.
Main Results:
- Socs-2 and Cis mRNA expression in rat liver is dependent on the presence of GH.
- GH was found to induce Cis mRNA expression in primary rat hepatocytes.
- Constitutive expression of Cis, but not Socs-2, significantly inhibited GH-induced transactivation of a Stat5-responsive reporter gene in BRL-4 cells.
Conclusions:
- Cis plays a functional role in the desensitization of GH-activated Jak/Stat5 signaling in rat liver cells.
- GH induction of Cis is a potential mechanism contributing to the sexually dimorphic GH signaling via Stat5b in the rat liver, influenced by secretion patterns.