INSULIN-LIKE GROWTH-FACTOR-I POTENTIATES PROTEIN-SYNTHESIS INDUCED BYTHYROTROPIN IN FRTL-5 CELLS - COMPARISON OF INDUCTION OF PROTEIN-SYNTHESIS AND DNA-SYNTHESIS

In FRTL-5 cells, we and others have shown that TSH and insulin-like gr owth factor-I (IGF-I) stimulate DNA synthesis synergistically. The pre sent study was undertaken to determine whether interaction between TSH and IGF-I also affects protein synthesis in this cell line, and if so by what mechanism. Quiescent cells were treated, with TSH and/or IGF- I and [H-3]valine incorporation into the acid-insoluble fraction was m easured as a parameter of protein synthesis. Similar to their effects on cell proliferation, TSH or IGF-I alone induced protein synthesis on ly slightly, but treatment with a combination of TSH and IGF-I (or ins ulin with about a 100-fold higher concentration than IGF-I) greatly in creased protein synthesis. The presence of IGF-I potentiated a TSH-con centration-dependent increase in protein synthesis and in DNA synthesi s. In addition, we observed this potentiation when the cells were trea ted with other CAMP-generating agents and CAMP analogues instead of TS H. We have shown that priming with TSH potentiated DNA synthesis induc ed by IGF-I, whereas pretreatment with IGF-I enhanced protein synthesi s induced by TSH. This observation suggested that protein synthesis an d DNA synthesis were potentiated through different mechanisms. From an analysis of CAMP production, it appears that the potentiation of prot ein synthesis may be explained by an IGF-I-dependent increase in CAMP production induced by TSH at least in part. On the other hand, IGF-I a nd TSH stimulated (alpha-aminoisobutyric acid (AIB) uptake synergistic ally, but RNA synthesis induced by IGF-I was depressed by TSH. From th ese results, we concluded that in FRTL-5 cells, IGF-I potentiated prot ein synthesis induced by TSH by means of complex mechanisms and the in teraction between IGF-I and cAMP-dependent pathways may also have a ph ysiological meaning in regulating protein anabolism.