Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-I concentrations.

Thissen, Jean-Paul;Underwood, Louis E;Maiter, Dominique;Maes, Marc;Ketelslegers, Jean-Marie;et.al.
(1991) Endocrinology — Vol. 128, n° 2, p. 885-890 (1991)

Files

No attached file found for this publication.

Details

Authors
  • Thissen, Jean-Paulorcid-logoUCLouvain
    Author
  • Underwood, Louis EDepartments of Pediatrics and Medicine, School of Medicine (J.P.T., L.E.U., D.R.C.), University of North Carolina Chapel Hill, North Carolina
    Author
  • Author
  • Maes, MarcUCLouvain
    Author
  • Ketelslegers, Jean-MarieUCLouvain
    Author
Show more
Abstract
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.
Affiliations

Citations

Thissen, J.-P., Underwood, L. E., Maiter, D., Maes, M., Clemmons, D. R., & Ketelslegers, J.-M. (1991). Failure of insulin-like growth factor-I (IGF-I) infusion to promote growth in protein-restricted rats despite normalization of serum IGF-I concentrations. Endocrinology, 128(2), 885-890. https://doi.org/10.1210/endo-128-2-885 (Original work published 1991)