Effect of dietary protein deprivation on insulin-like growth factor (IGF)-I and -II, IGF binding protein-2, and serum albumin gene expression in rat.
Circulating levels of insulin-like growth factor I (IGF-I) and serum albumin are decreased under conditions of chronic dietary protein limitation. To investigate the biochemical mechanism(s) involved in the regulation of IGF-I and serum albumin synthesis by dietary protein, we studied the effects of protein limitation on IGF-I and serum albumin gene expression in young growing rats maintained on isocaloric diets containing 20%, 12%, 8%, or 4% protein. Animals maintained on the 12%, 8%, or 4% protein diets exhibited slight, moderate, or severe growth deficiency, respectively, and a decreased abundance of hepatic IGF-I messenger RNA (mRNA). The decrease in IGF-I mRNA was most pronounced for the largest [7.7 kilobase (kb)] species, which was decreased by 87% in animals maintained on the 4% protein diet compared with animals on the 20% protein diet. The 0.9 kb species of IGF-I mRNA exhibited a smaller (46%) reduction in abundance in animals maintained on the 4% protein diet. The differential regulation of the 7.7 kb IGF-I mRNA species compared with the shorter IGF-I mRNA species suggests that a sequence or sequences within the long 3'-untranslated region of this mRNA species may play a role in regulating its abundance under conditions of protein limitation. Serum albumin mRNA was also decreased (by 62%) in the animals maintained on the 4% protein diet. The level of serum albumin gene transcription was not decreased in animals on the low protein diets, suggesting that nutrition regulates albumin mRNA at a posttranscriptional step. There was considerable animal-to-animal variability in the level of IGF-I gene transcription within each dietary group. The mean level of IGF-I gene transcription was decreased by 46% in the animals on the 4% protein diet compared with animals on the 20% protein diet, although this decrease was not statistically significant because of the animal-to-animal variability in IGF-I gene transcription within the dietary groups. Additional studies of brain RNA from animals on the four diets indicated that brain IGF-II mRNA was decreased by 57% in animals on the 4% protein diet. It has been demonstrated recently that expression of the gene for IGF binding protein-2 (IGFBP-2) is strongly induced in the liver of fasting animals. To investigate the possible regulation of the IGFBP-2 gene in the protein-limited animals, the abundance of liver and brain IGFBP-2 mRNA was analyzed in animals on the four diets.(ABSTRACT TRUNCATED AT 400 WORDS)
Straus
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DS
Biomedical Sciences Division, University of California, Riverside 92521-0121.
Takemoto
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CD
D000199:Actins / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D004044:Dietary Proteins / Q000008:administration & dosage; D005786:Gene Expression Regulation; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D009693:Nucleic Acid Hybridization; D011488:Protein Deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000235:genetics*; D013002:Somatomedins / Q000235:genetics*; D014158:Transcription, Genetic
D000199:Actins; D002352:Carrier Proteins; D004044:Dietary Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D012709:Serum Albumin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I