The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins

Abstract

Circulating signalling proteins have often been divided into hormones and cytokines, but it is increasingly being recognised that these substances have a number of common characteristics and mechanisms of action. This is clearly illustrated by the suppressor of cytokine signalling (SOCS) proteins which are increasingly seen as a central component of the regulation of the action of hormones and cytokines that signal through the cytokine receptor complex. The SOCS protein family is probably more extensive than currently recognised; its members may have differential tissue expression and their potency for suppressing cytokine signalling may vary. Recent knockout and transgenic studies in mice have highlighted the role that these proteins play in growth and skeletal development as well as in inflammation. Chronic inflammation is associated with altered growth and skeletal development, and it is possible that SOCS proteins may have an important role to play in mediating these effects.

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

“…An increasing amount of data has supported a connection between the innate immune system and the activity of the GH/insulin-like growth factor 1 (IGF1) axis (1,2,3,4). The vast majority of clinical and experimental studies have focused on stages with increased inflammation where it seems that chronic inflammation suppresses the GH/IGF1 axis (2,5,6,7,8,9).…”

Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and insulin resistance in zebrafish

“…SOCS proteins have been well recognized as negative regulators of JAK-STAT signaling (1,32). To confirm the physiological effects of socs1a depletion in zebrafish in vivo, the status of the activation of JAK-STAT signaling was analyzed.…”

“…First, protein tyrosine phosphatases can remove phosphate from receptors and activated STAT molecules. More recently, members from a small protein family identified as suppressors of cytokine signaling (SOCS) have been found to form negative feedback loops to inhibit JAK-STAT signaling (1). Based on mouse genetic studies, distinguishable physiological roles for several members of the SOCS family have been delineated.…”

DNA methylation in the tumor microenvironment

“…The methylation and downregulated expression of SOCS1 can activate STAT3 signaling, leading to high expression of insulin-like growth factor-1 (IGF-1) in CAFs. CAFs were shown to promote tumor progression and invasion through secreting the protumoral growth factor IGF-1 (Mueller and Fusenig, 2004;Ahmed and Farquharson, 2010). Vizoso et al (2015) identified hypermethylationassociated SMAD family member 3 (SMAD3) silencing in CAFs, which was associated with aberrant response to exogenous TGF-β1.…”