Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-I concentrations.
Dietary protein restriction in young rats induces GH resistance characterized by growth arrest and low serum insulin-like growth factor-I (IGF-I) concentrations. To determine whether the low serum IGF-I concentrations are responsible for the stunted growth, we infused 4-week-old protein-restricted rats with recombinant human IGF-I (300 micrograms/day) or rat GH (200 micrograms/100 g body wt/day) by osmotic minipump for 1 week. Despite the normalization of serum IGF-I concentrations by IGF-I infusion, carcass growth was not stimulated. In contrast, growth of the spleen and kidney was enhanced (+45% and +28%, respectively). Serum IGF-binding protein 3 (IGFBP-3), the principal carrier of IGF-I in the serum at this age, is decreased by 34% in protein-restricted animals and restored to normal by IGF-I infusion. Contrary to the selective effects of IGF-I on growth of protein-restricted rats, well nourished hypophysectomized rats infused with 150 micrograms/day recombinant human IGF-I showed a significant growth response, including carcass and organ growth and normalization of IGFBP-3 values. These responses indicate that our IGF-I preparation and mode of delivery were effective. We conclude that: 1) dietary protein restriction causes organ-specific resistance to the growth-promoting properties of exogenous IGF-I; 2) IGF-I mediates the stimulatory effects of growth hormone on IGFBP-3 synthesis; and 3) the absence of carcass growth in the presence of normal serum IGF-I concentrations during infusion of IGF-I suggests that the growth arrest that accompanies protein restriction is mediated in part by resistance to IGF-I.
Thissen
J P
JP
Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill 27599.
Underwood
L E
LE
Maiter
D
D
Maes
M
M
Clemmons
D R
DR
Ketelslegers
J M
JM
D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D006128:Growth / Q000187:drug effects; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D009994:Osmolar Concentration; D011488:Protein Deficiency / Q000097:blood / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D004044:Dietary Proteins; D007334:Insulin-Like Growth Factor I