Cis desensitizes GH induced Stat5 signaling in rat liver cells.

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.