Insulin-like growth factor-I (IGF-I) infusion into hypophysectomized or protein-deprived rats induces specific IGF-binding proteins in serum.

Clemmons, D. R. [Departments of Medicine and Pediatrics, University of North Carolina Chapel Hill, North Carolina (USA)] Thissen, Jean-Paul [UCL] Maes, Marc [UCL] Ketelslegers, Jean-Marie [UCL] Underwood, L. E.

The insulin-like growth factors (IGFs) are small peptides that are present in serum and extracellular fluids and stimulate the growth of many cell types. In extracellular fluids the IGFs are bound to carrier proteins that are believed to modify the biological actions of the IGFs. At least three structurally distinct IGF-binding proteins (IGF-BPs) have been identified, and the serum concentrations of one of these has been shown to be regulated by pituitary GH. We report here that this GH responsive protein [39,000-45,000 mol wt (Mr)] can be induced (7-fold) by infusion of IGF-I in hypophysectomized rats or (3.5-fold) in protein-deprived rats, whereas two other forms of IGF-BP (e.g. 31,000-34,000 and 24,000 Mr) showed no change in the hypophysectomized animals and minimal increases in the protein-deprived animals. Likewise, GH injections in hypophysectomized animals resulted in a 7-fold increase in the 39,000-45,000 Mr form and no change in the 31,000-34,000 and 24,000 Mr forms. The protein-deprived animals showed a 3.2-fold increase in the 39,000-45,000 Mr and 2.4- to 1.8-fold increases in the 31,000-34,000 and 24,000 Mr forms, respectively. Changes in the larger Mr IGF-BP in these experimental models are paralleled by changes in serum IGF-I, suggesting that the GH dependence of the former protein is mediated at least partially via IGF-I. Our findings also suggest that the secretion of IGF-I and at least one IGF-BP may be linked, providing a mechanism by which their extracellular fluid concentrations are coordinated. Because IGF-BPs are present in extracellular fluids and can modulate IGF-I-receptor interaction, induction of this protein may be an important mediator of IGF action.