Early changes in serum concentrations of somatomedin-C induced by dietary protein deprivation in rats: contributions of growth hormone receptor and post-receptor defects.
To define the mechanism(s) for the decrease of somatomedin concentrations in acute protein malnutrition, we have assessed the relationships between serum immunoreactive somatomedin-C/insulin-like growth factor-I (Sm-C/IGF-I), serum immunoreactive GH and total (MgCl2-treated homogenates) as well as free (water-treated homogenates) liver somatogenic (GH) binding sites in growing rats fed a 5% protein diet for 12 or 24 h and given an s.c. injection(s) of rat GH (rGH) or saline. Control rats were fed a 15% protein diet and injected with rGH or saline. After 12 and 24 h of protein restriction, body weight was 6.9 and 8.2% below controls respectively (P less than 0.001), while Sm-C/IGF-I concentrations were reduced by 58 and 66% respectively (P less than 0.001 vs controls). Serum GH concentrations were not affected by the low protein intake. Furthermore, injection(s) of 50-100 micrograms rGH failed to raise serum Sm-C/IGF-I concentrations in the protein-deficient animals. The number of total and free GH-binding sites was modestly (15-20%) decreased at 12 and 24 h in the protein-restricted rats. Serum Sm-C/IGF-I concentrations correlated weakly with free and total binding sites (r = 0.48 and 0.38 respectively). Affinity constants of GH-binding sites were not changed by protein restriction. The profound reduction in Sm-C/IGF-I concentrations within a few hours of beginning protein restriction, and the discordance between this reduction and the small decline in somatogenic binding sites, suggests that, in addition to GH receptor loss, a postreceptor defect may participate in the GH resistance occurring in the early stages of protein deficiency.
Maiter
D
D
Unité de Diabétologie et Nutrition, School of Medicine, University of Louvain, Brussels, Belgium.
Maes
M
M
Underwood
L E
LE
Fliesen
T
T
Gerard
G
G
Ketelslegers
J M
JM
D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D011485:Protein Binding; D011488:Protein Deficiency / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013002:Somatomedins / Q000097:blood*
D011986:Receptors, Somatotropin; D013002:Somatomedins; D015636:Magnesium Chloride; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008274:Magnesium