The interaction between IGF-I-dependent and other hormones-dependent signal pathways in cell growth and differentiation

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Studies were undertaken to determine the mechanism(s) by which thyroid stimulating hormone (TSH) and insulin-like growth factor-I (IGF-I) act synergistically to stimulate protein synthesis and DNA synthesis in FRTL-5 cells. The response of these cells to TSH and IGF-I greatly surpass the sum of the effects of the individual hormones when acting alone. Preincubation with IGF-I potentiates the effect of TSH on protein synthesis. On the contrary,after preincubation with TSH,FRTL-5 cells exhibited greatly increased response to the mitogenic activity of IGF-I.Furthermore,pretreatment of the cells for 24h with either TSH or other agents that elevate intracellular cAMP potentiated the IGF-I-dependent tyrosine phosphorylation (pp175 and pp95),and increased IGF-I-independent tyrosine phosphorylation(pp125, pp100 and pp80). These results suggest that a cAMP stimulus can be propagated through multiple pathways including enhancement of tyrosine phosphorylation. These phenomena were also observed in primary cultures of rat hepatocytes treated with cAMP-generating agents and insulin. The purification of pp175 from the lysates of FRTL-5 cells treated with Bt_2cAMP and IGF-I is in progress in our laboratory,using DEAE-ion exchange chromatography,anti-phosphotyrosine antibody conjugated Sepharose affinity chromatography,and SDS-polyacryl amide gel electrophoresis.