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)
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Thissen, Jean-PaulUCLouvain
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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
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., 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)