Autocrine secretion of insulin-like growth factor-I mediates growth hormone-stimulated DNA synthesis and proliferation in primary cultures of adult rat hepatocytes

The intracellular signaling pathway of growth hormone (GH)-stimulated DNA synthesis and proliferation was investigated in primary cultures adult rat hepatocytes. cell were detected hepatocyte parenchymal cells grown serum-free, defined medium containing GH (100 ng/ml). GH-stimulated almost completely blocked by TG101209 (10?6 M), a selective Janus kinase (JAK)2 inhibitor, U-73122 phospholipase C (PLC) monoclonal antibody to insulin-like factor-I (IGF-I) receptor ng/ml) or anti-secretion agents such as somatostatin M) BAPTA/AM (10?7 M). In addition, blocking antibodies IGF-I, but not transforming factor-?, inhibited GH-induced proliferation. IGF-I levels the culture increased rapidly versus baseline within 5 min response ng/ml), maximum level pg/ml) reached 20 after stimulation. Autocrine secretion into growth-inhibitory dose TG101209, U-73122, somatostatin, BAPTA/AM. These data indicate that proliferative mechanism action is mediated mainly through receptor/JAK2/PLC-stimulated increase autocrine cultured hepatocytes, followed stimulation 95 kDa tyrosine pathway.