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Evidence that pretranslational and translational defects decrease serum insulin-like growth factor-I concentrations
J P Thissen1, S Triest, B M Moats-Staats
1Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill 27599.
Endocrinology
|July 1, 1991
Summary
Dietary protein restriction impairs growth hormone response, lowering insulin-like growth factor-I (IGF-I). This study reveals protein restriction decreases IGF-I mRNA stability and suggests translational issues or increased clearance cause low IGF-I levels.
Area of Science:
- Endocrinology
- Molecular Biology
- Nutritional Science
Background:
- Dietary protein restriction is known to cause growth hormone (GH) resistance.
- This leads to decreased serum concentrations of insulin-like growth factor-I (IGF-I).
- The underlying molecular mechanisms, whether pretranslational or translational, remain unclear.
Purpose of the Study:
- To investigate the role of pretranslational and translational defects in the decline of serum IGF-I during protein restriction.
- To assess hepatic IGF-I messenger RNA (mRNA) abundance and the peptide response to exogenous GH in protein-restricted rats.
Main Methods:
- Hypophysectomized rats were fed either a protein-restricted (5% casein) or a protein-sufficient (15% casein) diet for one week.
- Both groups received exogenous rat GH injections.
- Hepatic IGF-I mRNA levels and serum IGF-I peptide concentrations were measured.
- Experiments were also conducted in intact rats subjected to protein restriction and treated with GH.
Main Results:
- Exogenous GH induced a comparable increase in hepatic IGF-I mRNA in both protein-restricted and sufficient groups.
- However, serum IGF-I levels failed to rise normally in protein-restricted rats.
- The decline of IGF-I mRNA was faster in protein-restricted rats.
- In intact rats, GH normalized IGF-I mRNA but not serum IGF-I levels.
Conclusions:
- The transcription of the liver IGF-I gene remains intact during protein restriction.
- Protein restriction likely decreases the stability of IGF-I mRNA.
- Low serum IGF-I concentrations in protein restriction may result from translational stalling of IGF-I mRNA or increased IGF-I clearance.