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Endocrinology, doi:10.1210/endo-128-2-885
Endocrinology Vol. 128, No. 2 885-890
Copyright © 1991 by the Endocrine Society.
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Failure of Insulin-Like Growth Factor-I (IGF-I) Infusion to Promote Growth in Protein-Restricted Rats Despite Normalization of Serum IGF-I Concentrations*

JEAN-PAUL THISSEN{dagger}, LOUIS E. UNDERWOOD, DOMINIQUE MAITER{dagger}, MARC MAES{ddagger}, DAVID R. CLEMMONS and JEAN-MARIE KETELSLEGERS

Departments of Pediatrics and Medicine, School of Medicine (J.P.T., L.E.U., D.R.C.), University of North Carolina Chapel Hill, North Carolina 27599
Unite de Diabetologie et de Nutrition, University of Louvain, School of Medicine (D.M., MM., J.M.K.) B-1200 Brussels, Belgium

Address all correspondence and requests for reprints to: Dr. Jean- Paul Thissen, Department of Pediatrics, CB 7220, 509 Burnett-Wornack Building, University of North Carolina, Chapel Hill, North Carolina 27599.

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 proteinrestricted rats with recombinant human IGF-I (300 µg/day) or rat GH (200 µg/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 µg/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. (Endocrinology 128: 885–890, 1991)

Footnotes

* This work was supported by grants from the Fonds de la Recherche Scientifique Medicale (3.4538.80) and NIH Research Grants HD-08299 and AG-02331.

{dagger} Research Assistants from the National Fund for Scientific Research (Belgium).

{ddagger} Département de Pédiatrie, Cliniques Universitaires St Luc, B-1200 Brussels, Belgium.

Received September 17, 1990.




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