Document Detail

Nutrient-hormone interaction in the ovine liver: methionine supply selectively modulates growth hormone-induced IGF-I gene expression.
MedLine Citation:
PMID:  12176673     Owner:  NLM     Status:  MEDLINE    
This study tested the hypothesis that specific amino acids are responsible for modulating the insulin-like growth factor-I (IGF-I) response to growth hormone (GH) in ovine hepatocytes. Cells were grown in media of defined amino acid composition, based on physiological concentrations (P.C.) of amino acids in sheep plasma. Relative to culture in 5 x P.C., amino acid limitation to 0.2 x P.C. had inhibitory effects on IGF-I RNA expression, peptide release and p70 S6 kinase phosphorylation (P<0.01 in each case). Limitation of methionine levels to 0.2 x P.C. against a background of 5 x P.C. for the other amino acids blocked GH-stimulated IGF-I peptide release and RNA expression, although basal expression was unaffected. In contrast, limitation of the other amino acids present in the culture medium had no effect on basal or GH-stimulated IGF-I expression. Selective methionine limitation to 0.2xP.C. levels had no effect on cellular or secretory protein synthesis rates relative to cells grown in complete 5 x P.C. medium but did cause a partial reduction in p70 S6 kinase phosphorylation, which was also observed when medium was selectively limited for other essential amino acids. The addition of rapamycin (5 ng/ml) to cells grown in 5xP.C. media completely abolished p70 S6 kinase phosphorylation (P<0.001), implicating mTOR in the response of S6 kinase phosphorylation to changing amino acid supply. By contrast, inclusion of rapamycin (100 ng/ml) had no effect on levels of IGF-I gene expression. These results indicate that methionine is the key limiting amino acid involved in the modulation of IGF-I expression in the ovine liver. This nutrient-hormone interaction is a highly selective phenomenon, occurring against a background of modest effects on general protein synthetic control. The partial inhibitory effects of methionine on mTOR activity are not sufficient to account for this selectivity of action.
A K Stubbs; N M Wheelhouse; M A Lomax; D G Hazlerigg
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of endocrinology     Volume:  174     ISSN:  0022-0795     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-14     Completed Date:  2002-10-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  335-41     Citation Subset:  IM    
Animal Biology Group/Aberdeen Centre for Energy Regulation and Obesity (ACERO), Department of Agriculture and Forestry, MacRobert Building, University of Aberdeen, 581 King Street, Aberdeen, AB24 5UA, UK.
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MeSH Terms
Analysis of Variance
Cells, Cultured
Enzyme Inhibitors / pharmacology
Gene Expression Regulation*
Growth Hormone / pharmacology*
Hepatocytes / metabolism*
Insulin-Like Growth Factor I / analysis,  genetics*
Methionine / metabolism*
Ribosomal Protein S6 Kinases / antagonists & inhibitors,  metabolism
Sirolimus / pharmacology
Reg. No./Substance:
0/Enzyme Inhibitors; 53123-88-9/Sirolimus; 63-68-3/Methionine; 67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone; EC Protein S6 Kinases

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