Type II Socs Family Members as Intracellular Feedback Inhibitors for Growth Hormone and Somatolactin in Grass Carp

This dissertation, "Type II SOCS Family Members as Intracellular Feedback Inhibitors for Growth Hormone and Somatolactin in Grass Carp" by Xue, Jiang, 姜雪, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled TYPE II SOCS FAMILY MEMBERS AS INTRACELLULAR FEEDBACK INHIBITORS FOR GROWTH HORMONE AND SOMATOLACTIN IN GRASS CARP Submitted by Jiang Xue for the degree of Doctor of Philosophy at The University of Hong Kong in September 2013 Suppressors of cytokine signaling (SOCS) are intracellular feedback repressors for JAK/STAT signaling coupled to cytokine receptors and can be classified into type I and II subfamilies according to their phylogenetic distribution and structural features. In recent years, SOCS have been identified in lower vertebrates including fish species. However, their functional studies are restricted to immune functions, and to date, little/no information is available regarding the role of SOCS in signal transduction and biological actions of pituitary hormones in non-mammalian models. Using grass carp as a model, the members of type II SOCS, SOCS1-3 and CISH, were cloned and their tissue expression profiles characterized. In primary cultures of carp hepatocytes and pituitary cells, the functionality of type II SOCS has been confirmed by endotoxin and cytokine induction of SOCS1-3 and CISH mRNA expression. In carp hepatocytes, besides triggering IGF-I and -II expression, growth hormone (GH) treatment could also elevate SOCS1-3 and CISH mRNA levels via JAK /STATs and MAPK cascades. Except for GH-induced SOCS3 responses, PI3K/Akt pathway was not involved in the corresponding responses of SOCS1-2 and CISH mRNA expression. In parallel studies in CHO cells with carp GH receptor expression, SOCS1-3 and CISH over-expression were found to inhibit JAK /STAT signaling coupled to GH receptor and GH-induced IGF-I promoter 2 5 activation. Furthermore, GH-induced IGF-I and -II mRNA expression in carp hepatocytes could be blocked actions probably were due to -induced SOCS1-3 and CISH expression mediated through IKK/NF B, JAK /STATs, MAPK and PI3K/Akt activation. Recently, somatolactin (SL), the latest member of GH/prolactin family, has been reported to have local pituitary actions and constitute the novel phenomenon of "SL autoregulation" in the carp pituitary. In carp pituitary cells, treatment with concurrent rises in SOCS1-3 and CISH transcript expression. Interestingly, Apparently, except for the lack of PI3K/Akt involvement in SOCS2 responses, the JAK /STAT, MAPK and PI3K/Akt activation. Using a 2 5 newly developed method for transfection in primary pituitary cell culture, SOCS1-3 and CISH over-expression were performed in carp pituitary cells and - - - - enhanced by insulin co-treatment, which presumably was caused by insulin - -induced SOCS1-3 and CISH expression. Besides, insulin alone was also effective in suppressing SOCS2 gene expression in carp pituitary cells via JAK /STATs and PI3K/Akt activation. Our findings, taken together, provide evidence that (i) type II SOCS can serve as feedback repressors for the hepatic actions of GH and pituitary actions of SL, and (ii) pituitary expression of type II SOCS can form a new facet for insulin modulation of pituitary functions. DOI: 10.5353/th_b5348330 Subjects: Somatotropin Cytokines - Physiological effect Ctenopharyngodon idella - Molecular genetics