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Dietary Protein Restriction Inhibits Growth Hormone-Induced DNA Synthesis without Impairing c-myc and c-Ha-ras Expression in the Liver of Hypophysectomized Rats^1,2,3,

Unité de Diabétologie et Nutrition, School of Medicine, University of Louvain, B-1200 Brussels, Belgium

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.

KEY WORDS: • proto-oncogenes • liver • rats • protein restriction • DNA synthesis

¹ Presented at the American Association for the Study of Liver Diseases Single Topic Symposium, "Liver Regeneration," June 24–27, 1993, at Airlie, VA [Triest, S., Thissen, J. P., Maiter, D., Mauerhoff, T. & Ketelslegers, J. M. (1993) Dietary protein restriction inhibits growth hormone-induced DNA synthesis without impairing c-myc and c-Ha-ras expression in the liver of hypophysectomized rats. Abstr. 35].

² Supported by grants from Nestec, Lausanne, Switzerland and from the Belgian National Fund for Scientific Research (grants "Hippocrate International" and nos. 3.4544.87 and 3.4559.93), Brussels, Belgium.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 13 September 1994. Revision accepted 31 January 1995.