STAT5b is required for GH-induced liver Igf-I gene expression

Although the increased expression of Igf-l in liver in response to GH is we ll characterized, the intracellular signaling pathways that mediate this ef fect have not been identified. Intracellular signaling molecules belonging to the Janus kinase-signal transducer and activator of transcription 5b (JA K2-STAT5b) pathway are activated by GH and have previously been shown to be required for sexually dimorphic body growth and the expression of liver cy tochrome P450 proteins known to be regulated by the gender-specific tempora l patterns of pituitary GH secretion. Here, we evaluate the role of STAT5b in GH activation of Igf-I by monitoring the induction of Igf-I mRNA in live rs of wild-type and Stat5b(-/)-mice stimulated with exogenous pulses of GH. GH induced the expression of liver Igf-l mRNA in hypophysectomized male wi ld-type, but not in hypophysectomized male Stat5b(-/-) mice, although the S tat5b(-/-) mice exhibit both normal liver GH receptor expression and strong GH induction of Cytokine-inducible SH2 protein (Cis), which is believed to contribute to the down-regulation of GH-induced liver STAT5b signaling. Th us, STAT5b plays an important and specific role in liver Igf-I gene express ion.