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.