Evidence that pretranslational and translational defects decrease serum insulin-like growth factor-I concentrations during dietary protein restriction.
Dietary protein restriction causes GH resistance and decreases serum insulin-like growth factor-I (IGF-I) concentrations. To determine whether pretranslational or translational defects are involved in the decline of serum IGF-I concentrations during protein restriction, we measured hepatic IGF-I mRNA abundance together with the serum IGF-I peptide response to exogenous GH after 1 week of protein restriction (5% casein in diet; P5) in hypophysectomized rats. We compared these responses with those of hypophysectomized rats fed a protein-sufficient diet (15% casein in diet; P15) and given exogenous GH. A single injection of rat GH (200 micrograms/100 g BW) produced a comparable IGF-I mRNA increment in both groups (at 6 h, 7.8 +/- 1.1 arbitrary units in P5 vs. 8.2 +/- 1.1 in P15), but failed to raise serum IGF-I normally in the P5 group (at 6 h, 90 +/- 15 ng/ml in P5 vs. 216 +/- 63 in P15; P less than 0.01). The post-GH decline of the 7.5-kilobase (kb) IGF-I mRNA abundance was faster in P5 than in P15 animals. In another experiment in intact rats subjected to protein restriction, injections of pharmacological doses of rat GH (400 micrograms/100 g BW.day) for 1 week restored liver IGF-I mRNA abundance to normal without normalization of serum IGF-I (403 +/- 91 vs. 713 +/- 53 ng/ml; P less than 0.01). Our data suggest that 1) the machinery involved in the transcription of the liver IGF-I gene is intact in protein-restricted rats, because these animals retain the ability to muster normal IGF-I mRNA responses to high doses of exogenous GH; 2) the stability of the 7.5-kb IGF-I mRNA is probably decreased by the protein restriction, as suggested by the faster decline of the 7.5-kb transcript in P5 than in P15 hypophysectomized rats; and 3) the discrepancy between normal liver IGF-I mRNA abundance and low serum and liver IGF-I peptide concentrations suggests that translational stalling of the IGF-I mRNAs or increased serum IGF-I clearance is involved in the low serum IGF-I concentrations during dietary protein restriction.
Thissen
J P
JP
Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill 27599.
Triest
S
S
Moats-Staats
B M
BM
Underwood
L E
LE
Mauerhoff
T
T
Maiter
D
D
Ketelslegers
J M
JM
D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011488:Protein Deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects
D004044:Dietary Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone