Dietary protein restriction inhibits growth hormone-induced DNA synthesis without impairing c-myc and c-Ha-ras expression in the liver of hypophysectomized rats.

Triest, S K Thissen, Jean-Paul [UCL] Maiter, Dominique [UCL] Mauerhoff, T. Ketelslegers, Jean-Marie [UCL]

Cellular proliferation is impaired by malnutrition, and the mechanisms responsible for this inhibitory effect are poorly understood. One possible mechanism might involve alterations of the cell cycle-associated proto-oncogene expression. To test this hypothesis, we studied the effects of dietary protein restriction on DNA synthesis and c-myc and c-Ha-ras proto-oncogene mRNA responses to growth hormone in the liver of hypophysectomized rats. In rats fed a normal protein diet (15% protein), growth hormone injection induced a sequential activation of c-myc expression (13 times the baseline value, after 1 h) and c-Ha-ras expression (two times the baseline value, after 6 h), which was followed by a stimulation of liver DNA synthesis (9 times the baseline value, after 24 and 36 h). In rats fed a protein-restricted diet (5% protein), growth hormone injection did not induce liver DNA synthesis after 24 or 36 h. However, the baseline level of c-myc mRNA was higher in protein-restricted than in rats fed a normal diet and that of c-Ha-ras mRNA was unaffected by protein restriction. Furthermore, the peak response of c-myc mRNA was more important in protein-restricted rats than in rats fed a normal diet, and the c-Ha-ras mRNA response to growth hormone injection was similar in both dietary groups. These results show that dietary protein restriction inhibits growth hormone-induced DNA synthesis without impairing c-myc and c-Ha-ras activation in the liver of hypophysectomized rats.