title: Dietary protein restriction inhibits growth hormone-induced DNA synthesis without impairing c-myc and c-Ha-ras expression in the liver of hypophysectomized rats.
abstract: 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.
authors.affiliation: Unité de Diabétologie et Nutrition, School of Medicine, University of Louvain, Brussels, Belgium.
authors.forename: S K
authors.initials: SK
authors.lastname: Triest
authors.forename: J P
authors.initials: JP
authors.lastname: Thissen
authors.forename: D M
authors.initials: DM
authors.lastname: Maiter
authors.forename: T
authors.initials: T
authors.lastname: Mauerhoff
authors.forename: J M
authors.initials: JM
authors.lastname: Ketelslegers
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000096:biosynthesis*; D018753:Diet, Protein-Restricted; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016259:Genes, myc; D011905:Genes, ras; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis / Q000235:genetics*; D009929:Organ Size; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA; D015689:Oncogene Protein p21(ras)