Growth Hormone (GH) is a major regulator of statural growth and metabolism. Changes in gene expression and in their regulatory transcription factors often underlie the physiological responses to GH. Recent insights in understanding GH signaling indicate that the interaction of GH with GH receptors on target cells initiates multiple signaling cascades that culminate in changes in transcription factors in the nucleus. Through analysis of profiles of GH-regulated genes, we find that in addition to well-recognized Stat5-mediated signaling, GH utilizes Ras/MAPK-mediated signaling to regulate the phosphorylation and function of C/EBP-CREB family transcription factors, which in turn modulate multiple genes in response to GH. Among these, GH-induced Ras/MAPK signaling mediates the phosphorylation of C/EBP beta, which contributes to the recruitment of the co-activator p300 in stimulating these genes. Thus, multiple signaling pathways are involved in mediating the ability of GH to regulate genes associated with its diverse physiological responses.
