Endocrinology, Vol 129, 149-157, Copyright © 1991 by Endocrine Society

ARTICLES

Differential regulation of the insulin-like growth factors (IGF-I and - II) and IGF binding proteins during malnutrition in the neonatal rat

SM Donovan, LC Atilano, RL Hintz, DM Wilson and RG Rosenfeld
Department of Pediatrics, Stanford University Medical Center, California 94305.

Insulin-like growth factor (IGF)-I and -II are known to play a major role in fetal and early postnatal growth. The IGF binding proteins (IGFBPs) are thought to be important in modulating the actions of the IGFs. In this paper, the effect of malnutrition in the neonatal rat on serum IGFs and IGFBPs and hepatic IGFBP messenger (m) RNA was examined. Control (C) dams (n = 9) were allowed ad libitum intake, whereas restricted (R) dams (n = 9) were limited to 50% of ad libitum intake throughout lactation, which results in decreased milk production and malnutrition of pups suckling on restricted dams. A subset of pups were cross-fostered from the R-dams to the C-dams from days 15-19 postpartum (PP) to investigate the effect of nutritional repletion (refed). Pups were killed on days 8, 12, 15, and 19 PP and liver and blood collected. Serum IGF-I and -II concentrations were measured by RIA after acid- chromatography to remove IGFBPs. Serum IGFBPs were characterized by Western ligand blot. Hepatic mRNA for IGFBP-1, -2, and -3 were determined by northern analysis. Body weight (BW) of R-pups was significantly less than C-pups by day 10 PP (P less than or equal to 0.05), and mean BW at day 19 was 56% of the C-pups. Refeeding from days 15-19 resulted in a significantly greater rate of growth vs. R-pups (3.2 vs. 0.9 g/day), and mean BW of refed pups at day 19 PP was 75% of C-pups. Malnutrition caused a significant reduction in both serum IGF-I and -II after day 12 PP, while causing an elevation in serum IGFBP-2. IGFBP-1 and IGFBP-2 mRNA expression were not significantly affected at days 8 and 12, but were elevated in livers of day 15 and 19 pups. Malnutrition caused a delay in the development shift from IGFBP-2 to IGFBP-3, which normally occurs between day 15 and 19 in the rat. Refeeding raised serum IGF-I and -II levels to those found in the C- pups and a trend toward normalization of IGFBP profiles. In conclusion, IGFs and IGFBPs are differentially regulated during neonatal malnutrition. The decrease in IGF peptide and induction of IGFBP-1 and - 2 may provide protective mechanisms by inhibiting growth during malnutrition.

This article has been cited by other articles:

				V. E. DeMambro, D. R. Clemmons, L. G. Horton, M. L. Bouxsein, T. L. Wood, W. G. Beamer, E. Canalis, and C. J. Rosen Gender-Specific Changes in Bone Turnover and Skeletal Architecture in Igfbp-2-Null Mice Endocrinology, May 1, 2008; 149(5): 2051 - 2061. [Abstract] [Full Text] [PDF]

				T. A. Davis, M. L. Fiorotto, D. G. Burrin, R. C. Vann, P. J. Reeds, H. V. Nguyen, P. R. Beckett, and J. A. Bush Acute IGF-I infusion stimulates protein synthesis in skeletal muscle and other tissues of neonatal pigs Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E638 - E647. [Abstract] [Full Text] [PDF]

				T. J. Maures and C. Duan Structure, Developmental Expression, and Physiological Regulation of Zebrafish IGF Binding Protein-1 Endocrinology, July 1, 2002; 143(7): 2722 - 2731. [Abstract] [Full Text] [PDF]

				W. M. Naranjo, S. Yakar, M. Sanchez-Gomez, A. U. Perez, J. Setser, and D. LERoith Protein Calorie Restriction Affects Nonhepatic IGF-I Production and the Lymphoid System: Studies Using the Liver-Specific IGF-I Gene-Deleted Mouse Model Endocrinology, June 1, 2002; 143(6): 2233 - 2241. [Abstract] [Full Text] [PDF]

				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]

				L. Goya, A. de la Puente, S. Ramos, M. A. Martin, F. Escriva, C. Alvarez, and A. M. Pascual-Leone Regulation of IGF-I and -II by Insulin in Primary Cultures of Fetal Rat Hepatocytes Endocrinology, December 1, 2001; 142(12): 5089 - 5096. [Abstract] [Full Text] [PDF]

				T. Matsukawa, Y. Inoue, Y. Oishi, H. Kato, and T. Noguchi Up-Regulation of Upstream Stimulatory Factors by Protein Malnutrition and Its Possible Role in Regulation of the IGF-Binding Protein-1 Gene Endocrinology, November 1, 2001; 142(11): 4643 - 4651. [Abstract] [Full Text] [PDF]

				A. De la Puente, L. Goya, S. Ramos, M. A. Martin, C. Alvarez, F. Escriva, and A. M. Pascual-Leone Effects of experimental diabetes on renal IGF/IGFBP system during neonatal period in the rat Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1067 - F1076. [Abstract] [Full Text] [PDF]

				R. J Playford, C. E Macdonald, and W. S Johnson Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders Am. J. Clinical Nutrition, July 1, 2000; 72(1): 5 - 14. [Abstract] [Full Text] [PDF]

				L. Goya, A. de la Puente, S. Ramos, M. A. Martin, F. Escriva, and A. M. Pascual-Leone Regulation of Insulin-like Growth Factor-I and -II by Glucose in Primary Cultures of Fetal Rat Hepatocytes J. Biol. Chem., August 27, 1999; 274(35): 24633 - 24640. [Abstract] [Full Text] [PDF]

				F. A. Simmen, L. Badinga, M. L. Green, I. Kwak, S. Song, and R. C. M. Simmen The Porcine Insulin-Like Growth Factor System: At the Interface of Nutrition, Growth and Reproduction J. Nutr., February 1, 1998; 128(2): 315 - 315. [Abstract] [Full Text]

				W. J. Smith, L. E. Underwood, L. Keyes, and D. R. Clemmons Use of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein Measurements to Monitor Feeding of Premature Infants J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3982 - 3988. [Abstract] [Full Text] [PDF]

				B. Boersma and J. M. Wit Catch-up Growth Endocr. Rev., October 1, 1997; 18(5): 646 - 661. [Abstract] [Full Text]