Role of IGF-I in the intracellular signaling pathway of growth hormone-stimulated hepatocyte proliferation

Growth hormone (GH) is known to stimulate liver regeneration in 70% partially hepatectomized rats in vivo. Because complex involvement by multiple factors is unavoidable in in vivo experimental systems, clear interpretation becomes almost impossible when attempting to study the detailed mechanism of action. Therefore, we used a simpler, in vitro experimental system of primary cultured liver parenchymal cells to study the proliferation-stimulating effect of GH and its associated intracellular signal transduction mechanism from the GH receptor (GHR) to the nucleus. Many small molecular-targeted (specific signal transduction inhibitors) and large molecular-targeted agents (biological products and monoclonal antibodies) have now become available as pharmacological tools for research, and such agents enable a very detailed analysis of the mechanism underlying GH-induced stimulation of hepatic parenchymal cell proliferation. Consequently, we discovered that GH stimulates the proliferation of primary cultured mature rat liver parenchymal cells. We also found that the GH-induced stimulation of hepatic parenchymal cell proliferation is mediated by insulin-like growth factor-I (IGF-I), which is secreted by an autocrine mechanism.第一著者表記変更 Kurihara, Kazaki→Kurihara, Kazuk