Endocrinology, Vol 128, 885-890, Copyright © 1991 by Endocrine Society

ARTICLES

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

JP Thissen, LE Underwood, D Maiter, M Maes, DR Clemmons and JM Ketelslegers
Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill 27599.

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.

This article has been cited by other articles:

				M. Katsumata, S. Kawakami, Y. Kaji, R. Takada, and M. J. Dauncey Differential Regulation of Porcine Hepatic IGF-I mRNA Expression and Plasma IGF-I Concentration by a Low Lysine Diet J. Nutr., April 1, 2002; 132(4): 688 - 692. [Abstract] [Full Text] [PDF]

				S. Bourrin, P. Ammann, J. P. Bonjour, and R. Rizzoli Dietary Protein Restriction Lowers Plasma Insulin-Like Growth Factor I (IGF-I), Impairs Cortical Bone Formation, and Induces Osteoblastic Resistance to IGF-I in Adult Female Rats Endocrinology, September 1, 2000; 141(9): 3149 - 3155. [Abstract] [Full Text] [PDF]

				J. C. D. Filho, S. J. Hazel, B. Anderstam, J. Bergstrom, M. Lewitt, and K. Hall Effect of protein intake on plasma and erythrocyte free amino acids and serum IGF-I and IGFBP-1 levels in rats Am J Physiol Endocrinol Metab, October 1, 1999; 277(4): E693 - E701. [Abstract] [Full Text] [PDF]

				J. Frystyk, P. J. D. Delhanty, C. Skjarbak, and R. C. Baxter Changes in the circulating IGF system during short-term fasting and refeeding in rats Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E245 - E252. [Abstract] [Full Text] [PDF]

				A. J. Kee, R. C. Baxter, A. R. Carlsson, and R. C. Smith Parenteral amino acid intake alters the anabolic actions of insulin-like growth factor I in rats Am J Physiol Endocrinol Metab, July 1, 1999; 277(1): E63 - E72. [Abstract] [Full Text] [PDF]

				G. GAYAN-RAMIREZ, F. VANDERHOYDONC, G. VERHOEVEN, and M. DECRAMER Acute Treatment with Corticosteroids Decreases IGF-1 and IGF-2 Expression in the Rat Diaphragm and Gastrocnemius Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 283 - 289. [Abstract] [Full Text]

				J. Zhang, D. Chrysis, and L. E. Underwood Reduction of Hepatic Insulin-Like Growth Factor I (IGF-I) Messenger Ribonucleic Acid (mRNA) during Fasting Is Associated with Diminished Splicing of IGF-I Pre-mRNA and Decreased Stability of Cytoplasmic IGF-I mRNA Endocrinology, November 1, 1998; 139(11): 4523 - 4530. [Abstract] [Full Text] [PDF]

				S. Jain, D. W. Golde, R. Bailey, and M. E. Geffner Insulin-Like Growth Factor-I Resistance Endocr. Rev., October 1, 1998; 19(5): 625 - 646. [Abstract] [Full Text]

				J. C. Achermann, K. Hamdani, P. C. Hindmarsh, and C. G. D. Brook Birth Weight Influences the Initial Response to Growth Hormone Treatment in Growth Hormone-insufficient Children Pediatrics, August 1, 1998; 102(2): 342 - 345. [Abstract] [Full Text] [PDF]

				A. Carrillo, R. Rising, R. Tverskaya, and F. Lifshitz Effects of Exogenous Recombinant Human Growth Hormone on an Animal Model of Suboptimal Nutrition J. Am. Coll. Nutr., June 1, 1998; 17(3): 276 - 281. [Abstract] [Full Text] [PDF]

				J. Zhang, R. E. Whitehead Jr., and L. E. Underwood Effect of Fasting on Insulin-Like Growth Factor (IGF)-IA and IGF-IB Messenger Ribonucleic Acids and Prehormones in Rat Liver Endocrinology, August 1, 1997; 138(8): 3112 - 3118. [Abstract] [Full Text] [PDF]