The phospholipase C-InsP3 pathway is involved in calcium mobilization induced by growth hormone in hepatocytes

We investigated the effects of bovine GH (bGH) on Ca(2+) handling, phospholipase C (PLC) activation and inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] formation in hepatocytes. bGH generates oscillations in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in single male rat hepatocytes microinjected with the photoprotein aequorin. In the absence of extracellular Ca(2+) these transients persisted for more than 10 min indicating a requirement for intracellular Ca(2+). Treatment of the hepatocyte with the phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor U-73122 removed the oscillations. These results suggest bGH-induced oscillations are due to PLC activation and generation of Ins(1,4,5)P(3). We measured the mass of Ins(1,4,5)P(3) in freshly isolated hepatocyte suspensions in response to bGH, and vasopressin as a control. Both agonists rapidly increased the levels of Ins(1,4,5)P(3). This is the first study to indicate that early events in the signal transduction pathways mediated by GH in hepatocytes involve intracellular Ca(2+) mobilization via activation of a PI-PLC and subsequent Ins(1,4,5)P(3) production.