STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in theliver

Suppressor of cytokine signalling (SOCS) proteins act as part of a classica l negative feedback loop regulating cytokine signal transduction. Expressio n of SOCS proteins is induced in response to cytokines and down-regulates t he cytokine signal by inhibiting the JAK/STAT pathway. Growth hormone (GH) was previously shown to induce strong transient expression of SOCS-3 and to a lesser extent CIS, SOCS-1 and SOCS-2 in mouse liver (Adams, T.E., Hansen , J.A., Starr, R., Nicola, N.A., Hilton, D.J., Billestrup, N., 1998. Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of,cytokine receptor signalling. J. Biol. Chem. 273, 1285 -1287.). In this work we have compared GH-induced SOCS gene expression in w ild-type and STAT5b-deficient mice, and show that: STAT5b is required for t he induction of SOCS-2 and SOCS-3 in liver. In contrast, the absence of STA T5b has no effect on the GH-induced expression of CIS and SOCS-2 mRNA in th e mammary gland. Suprisingly, there is no activation of SOCS-3 expression i n mammary glands of wild-type and STAT5b mutant mice following GH administr ation. These results highlight both tissue- and factor-specific differences in the regulation of SOCS gene expression by STAT5a/b. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.