Nutritional and Tissue Specificity of IGF-I and IGFBP-2 Gene Expression in Growing Chickens - A Review -

  • Kita, K. (Graduate School of Bioagricultural Sciences, Nagoya University) ;
  • Nagao, K. (Graduate School of Bioagricultural Sciences, Nagoya University) ;
  • Okumura, J. (Nagoya Bunri University)
  • Published : 2005.05.01


Nutritional regulation of gene expression associated with growth and feeding behavior in avian species can become an important technique to improve poultry production according to the supply of nutrients in the diet. Insulin-like growth factor-I (IGF-I) found in chickens has been characterized to be a 70 amino acid polypeptide and plays an important role in growth and metabolism. Although it is been well known that IGF-I is highly associated with embryonic development and post-hatching growth, changes in the distribution of IGF-I gene expression throughout early- to late-embryogenesis have not been studied so far. We revealed that the developmental pattern of IGF-I gene expression during embryogenesis differed among various tissues. No bands of IGF-I mRNA were detected in embryonic liver at 7 days of incubation, and thereafter the amount of hepatic IGF-I mRNA was increased from 14 to 20 days of incubation. In eyes, a peak in IGF-I mRNA levels occurred at mid-embryogenesis, but by contrast, IGF-I mRNA was barely detectable in the heart throughout all incubation periods. In the muscle, no significant difference in IGF-I gene expression was observed during different stages of embryogenesis. After hatching, hepatic IGF-I gene expression as well as plasma IGF-I concentration increases rapidly with age, reaches a peak before sexual maturity, and then declines. The IGF-I gene expression is very sensitive to changes in nutritional conditions. Food-restriction and fasting decreased hepatic IGF-I gene expression and refeeding restored IGF-I gene expression to the level of fed chickens. Dietary protein is also a very strong factor in changing hepatic IGF-I gene expression. Refeeding with dietary protein alone successfully restored hepatic IGF-I gene expression of fasted chickens to the level of fed controls. In most circumstances, IGF-I makes a complex with specific high-affinity IGF-binding proteins (IGFBPs). So far, four different IGFBPs have been identified in avian species and the major IGFBP in chicken plasma has been reported to be IGFBP-2. We studied the relationship between nutritional status and IGFBP-2 gene expression in various tissues of young chickens. In the liver of fed chickens, almost no IGFBP-2 mRNA was detected. However, fasting markedly increased hepatic IGFBP-2 gene expression, and the level was reduced after refeeding. In the gizzard of well-fed young chickens, IGFBP-2 gene expression was detected and fasting significantly elevated gizzard IGFBP-2 mRNA levels to about double that of fed controls. After refeeding, gizzard IGFBP-2 gene expression decreased similar to hepatic IGFBP-2 gene expression. In the brain, IGFBP-2 mRNA was observed in fed chickens and had significantly decreased by fasting. In the kidney, IGFBP-2 gene expression was observed but not influenced by fasting and refeeding. Recently, we have demonstrated in vivo that gizzard and hepatic IGFBP-2 gene expression in fasted chickens was rapidly reduced by intravenous administration of insulin, as indicated that in young chickens the reduction in gizzard and hepatic IGFBP-2 gene expression in vivo stimulated by malnutrition may be, in part, regulated by means of the increase in plasma insulin concentration via an insulin-response element. The influence of dietary protein source (isolated soybean protein vs. casein) and the supplementation of essential amino acids on gizzard IGFBP-2 gene expression was examined. In both soybean protein and casein diet groups, the deficiency of essential amino acids stimulated chickens to increase gizzard IGFBP-2 gene expression. Although amino acid supplementation of a soybean protein diet significantly decreased gizzard IGFBP-2 mRNA levels, a similar reduction was not observed in chickens fed a casein diet supplemented with amino acids. This overview of nutritional regulation of IGF-I and IGFBP-2 gene expression in young chickens would serve for the establishment of the supply of nutrients to diets to improve poultry production.



  1. Allander, S. V., M. Coleman, H. Luthman and D. R. Powell. 1997. Chicken insulin-like growth factor binding protein (IGFBP)-5: conservation of IGFBP-5 structure and expression during evolution. Comp. Biochem. Physiol. 116B:477-483.
  2. Armstrong, D. G., C. O. McKay, D. J. Morrell and C. Goddard. 1989. Insulin-like growth factor-I binding proteins in serum from the domestic fowl. J. Endocrinol. 120:373-378.
  3. Baker, J., J. P. Liu, E. J. Robertson and A. Efstratiadis. 1993. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75:73-82.
  4. Ballard, F. J., R. J. Johnson, P. C. Owens, G. L. Francis, F. Z. Upton, J. P. McMurtry and J. C. Wallace. 1990. Chicken insulin-like growth factor-I: Amino acid sequence, radioimmunoassay, and plasma levels between strains and during growth. Gen. Comp. Endocrinol. 79:459-468.
  5. Bornfeldt, K. E., H. J. Arnqvist, B. Enberg, L. S. Mathews and G. Norstedt. 1989. Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues. J. Endocrinol. 122:651-656
  6. Dawe, S. R., G. L. Francis, J. P. McNamara, J. C. Wallace and F. J. Ballard. 1988. Purification, partial sequences and properties of chicken insulin-like growth factors. J. Endocrinol. 117:173-181.
  7. Elgin, R. G., W. H. Jr. Busby and D. R. Clemmons. 1987. An insulin-like growth factor (IGF) binding protein enhances the biologic response to IGF-I. Proc. Natl. Acad. Sci. USA. 84:3254-3258.
  8. Fawcett, D. H. and G. Bulfield. 1990. Molecular cloning, sequence analysis and expression of putative chicken insulin-like growth factor-I cDNAs. Domest. Anim. Endocrinol. 7:383-393.
  9. Francis, G. L., J. P. McMurtry, R. J. Johnson and F. J. Ballard. 1990. Plasma clearance of chicken and human insulin-like growth factor-I and their association with circulating binding proteins in chickens. J. Endocrinol. 124:361-370.
  10. Germain-Lee, E. L., M. Janicot, R. Lammers, A. Ullrich and S. J. Casella. 1992. Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II. Biochem. J. 281:413-417.
  11. Goodridge, A. G., D. A. Fantozzi, S. A. Klautky, X. J. Ma, C. Roncero and L. M. Salati. 1991. Nutritional and hormonal regulation of genes for lipogenic enzymes. Proc. Nutr. Soc. 50:115-122.
  12. Goodridge, A. G., S. A. Klautky, D. A. Fantozzi, R. A. Baillie, D. W. Hodnett, W. Chen, D. C. Thurmond, G. Xu and C. Roncero. 1996. Nutritional and hormonal regulation of expression of the gene for malic enzyme. Prog. Nucleic Acid Res. Mol. Biol. 52:89-122.
  13. Gurney, A. L., E. A. Park, J. Liu, M. Giralt, M. M. McGrane, Y. M. Patel, D. R. Crawford, S. E. Nizielski, S. Savon and R. W. Hanson. 1994. Metabolic regulation of gene transcription. J. Nutr. 124(8 Suppl):1533S-1539S.
  14. Hoeflich, A., M. Wu, S. Mohan, J. Foll, R. Wanke, T. Froehlich, G. L. Arnold, H. Lahm, H. J. Kolb and E. Wolf. 1999. Overexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postneonatal body weight gain. Endocrinol. 140:5488-5496.
  15. Horigome, T. and Y. S. Cho. 1992. Dietary casein and soybean protein affect the concentrations of serum cholesterol, triglyceride and free amino acids in rats. J. Nutr. 122:2273-2282
  16. Houston, B. and I. E. O'Neill. 1991. Insulin and growth hormone act synergistically to stimulate insulin-like growth factor-I production by cultured chicken hepatocytes. J. Endocrinol. 128: 389-393.
  17. Huybrechts, L. M., D. B. King, T. J. Lauterio, J. Marsh and C. G. Scanes. 1985. Plasma concentration of somatomedin-C in hypophysectomized, dwarf and intact growing domestic fowl as determined by heterologous radioimmunoassay. J. Endocrinol. 104:233-239.
  18. Johnson, R. J., J. P. McMurtry and F. J. Ballard. 1990. Ontogeny and secretory pattern of plasma insulin-like growth factor-I concentrations in meat-type chickens. J. Endocrinol. 124:81-87.
  19. Jousse, C., A. Bruhat, M. Ferrara and P. Fafournoux. 1998. Physiological concentration of amino acids regulates insulinlike growth factor-binding protein 1 expression. Biochem. J. 334:147-153.
  20. Kaiya, H., S. Van Der Geyten, M. Kojima, H. Hosoda, Y. Kitajima, M. Matsumoto, S. Geelissen, V. M. Darras and K. Kangawa. 2002. Chicken ghrelin: purification, cDNA cloning and biological activity. Endocrinol. 143:3454-3463.
  21. Kajimoto, Y. and P. Rotwein. 1989. Structure and expression of a chicken insulin-like growth factor I precursor. Mol. Endocrinol. 3:1907-1913.
  22. Kajimoto, Y. and P. Rotwein. 1991. Structure of the chicken insulin-like growth factor I gene reveals conserved promoter elements. J. Biol. Chem. 266:9724-9731.
  23. Ketelslegers, J. M., D. Maiter, M. Maes, L. E. Underwood and J. P. Thissen. 1996. Nutritional regulation of the growth hormone and insulin-like growth factor-binding proteins. Horm. Res. 45:252-257.
  24. Kikuchi, K., F. C. Buonomo, Y. Kajimoto and P. Rotwein. 1991. Expression of insulin-like growth factor-I during chicken development. Endocrinol. 128:1323-1328.
  25. Kita, K., K. Hangsanet and J. Okumura. 1997a. Changes in hepatic insulin-like growth factor-I and $\beta$-actin mRNA levels in chickens during early stages of growth. Anim. Sci. Tech. (Jpn.) 68:752-755.
  26. Kita, K., K. Hangsanet and J. Okumura. 1998a. Influence of refeeding of protein, carbohydrate and fat on hepatic insulinlike growth factor-I level in fasted chicks. Asian-Aust. J. Anim. Sci. 11:245-248.
  27. Kita, K., K. Hangsanet, T. Shibata, M. A. Conlon, T. Sasaki, N. Saito and J. Okumura. 1998b. Refeeding increases hepatic insulin-like growth factor-I (IGF-I) gene expression and plasma IGF-I concentration in fasted chicks. Br. Poult. Sci. 39: 679-682.
  28. Kita, K., J. Iwata, T. Shibata, M. A. Conlon and J. Okumura. 1997b. Influence of fasting on plasma insulin-like growth factor-I concentration in chickens at early stages of growth. Jpn. Poult. Sci. 34:410-413.
  29. Kita, K., M. Miyazaki and J. Okumura. 1996a. Influence of fooddeprived chicken serum on protein synthesis of chicken embryo fibroblasts. Jpn. Poult. Sci. 33:339-346.
  30. Kita, K., K. Nagao, N. Taneda, Y. Inagaki, K. Hirano, T. Shibata, M. Aman Yaman, M. A. Conlon and J. Okumura. 2002a. Insulin-like growth factor binding protein-2 gene expression can be regulated by diet manipulation in several tissues of young chickens. J. Nutr. 132:145-151.
  31. Kita, K., C. Noda, K. Miki, K. Kino and J. Okumura. 2000. Relationship of IGF-I mRNA levels to tissue development in chicken embryos of different strains. Asian-Aust. J. Anim. Sci. 13:1653-1658.
  32. Kita, K. and J. Okumura. 1999. Dietary protein levels alter plasma insulin-like growth factor-I concentration of chicks. Jpn. Poult. Sci. 36:25-30.
  33. Kita, K., T. Shibata, K. Nagao, J. Hwangbo and J. Okumura. 2002b. Effects of refeeding with protein-free diets supplemented with various essential amino acids on the plasma insulin-like growth factor-I concentration in fasted young chickens. Asian-Aust. J. Anim. Sci. 15:406-409.
  34. Kita, K., F. M. Tomas, P. C. Owens, S. E. Knowles, B. E. Forbes, Z. Upton, R. Hughes and F. J. Ballard. 1996b. Influence of nutrition on hepatic IGF-I mRNA levels and plasma concentrations of IGF-I and IGF-II in meat-type chickens. J. Endocrinol. 149:181-190.
  35. Kojima, M., H. Hosoda, Y. Date and K. Kangawa. 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660.
  36. Leili, S., F. C. Buonomo and C. G. Scanes. 1997. The effects of dietary restriction on insulin-like growth factor (IGF)-I and II, and IGF-binding proteins in chickens. Proc. Soc. Exp. Biol. Med. 216:104-111.
  37. Liu, J. P., J. Baker, A. S. Perkins, E. J. Robertson and A. Efstratiadis. 1993. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75:59-72.
  38. Lowe, W. L. Jr., M. Adamo, H. Werner, S. T. Roberts, Jr. and D. LeRoith. 1989. Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding. J. Clin. Invest. 84:619-626.
  39. Margot, J. B., C. Binkert, J. L. Mary, J. Landwehr, G. Heinrich and J. Schwander. 1989. A low molecular weight insulin-like growth factor binding protein from rat: cDNA cloning and tissue distribution of its messenger RNA. Mol. Endocrinol. 3:1053-1060.
  40. McGuinness, M. C. and L. A. Cogburn. 1990. Measurement of developmental changes in plasma insulin-like growth factor-I levels of broiler chickens by radioreceptor assay and radioimmunoassay. Gen. Comp. Endocrinol. 79:446-458.
  41. McMurtry, J. P., G. L. Francis, Z. Upton, P. E. Walton, G. Rosselot, T. J. Caperna and D. M. Brocht. 1996. Plasma clearance and tissue distribution of labelled chciken and human IGF-I and IGF-II in the chicken. J. Endocrinol. 150:149-160.
  42. Morishita, D., K. Sasaki, M. Wakita and S. Hoshino. 1993. Effect of fasting on serum insulin-like growth factor-I (IGF-I) levels and IGF-I binding activity in cockerels. J. Endocrinol. 139:363-370.
  43. Nagao, K., M. Aman Yaman, A. Murai, T. Sasaki, N. Saito, J. Okumura and K. Kita. 2001. Insulin administration suppresses an increase in insulin-like growth factor binding protein-2 gene expression stimulated by fasting in the chicken. Br. Poult. Sci. 42:501-504
  44. O'Neill, I. E., B. Houston and C. Goddard. 1990. Stimulation of insulin-like growth factor I production in primary cultures of chicken hepatocytes by chicken growth hormone. Mol. Cell. Endocrinol. 70:41-47.
  45. Pao, C. I., P. K. Farmer, S. Begovic, B. C. Villafuerte, G. J. Wu, D. G. Robertson and L. S. Phillips. 1993. Regulation of insulinlike growth factor-I (IGF-I) and IGF-binding protein 1 gene transcription by hormones and provision of amino acids in rat hepatocytes. Mol. Endocrinol. 7:1561-1568
  46. Patel, S., P. A. Lochhead, G. Rena, S. Fumagalli, M. Pende, S. C. Kozma, G. Thomas and C. Sutherland. 2002. Insulin regulation of insulin-like growth factor-binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity. J. Biol. Chem. 277:9889-9895.
  47. Rosebrough, R. W. and J. P. McMurtry. 1993. Protein and energy relationship in the broiler chicken. 11. Effects of protein quantity and quality on metabolism. Br. J. Nutr. 70:667-678.
  48. Rosebrough, R. W., J. P. McMurtry and R. Vasilatos-Younken. 1992a. In vitro lipid metabolism, growth and metabolic hormone concentrations in hyperthyroid chickens. Br. J. Nutr. 68:667-676.
  49. Rosebrough, R. W., J. P. McMurtry and R. Vasilatos-Younken. 1992b. Metabolic and hormonal effects of feeding chickens thyroxine and diets containing varied calorie to protein ratios. Nutr. Res. 12:77-87.
  50. Rosebrough, R. W., A. D. Mitchel and J. P. McMurtry. 1996. Dietary crude protein changes rapidly alter metabolism and plasma insulin-like growth factor I concentrations in broiler chickens. J. Nutr. 126:2888-2898.
  51. Roth, R. A. 1988. Structure of the receptor for insulin-like growth factor II: the puzzle amplified. Sci. 239:1269-1271.
  52. Rutanen, E. M., F. Pekonen and T. Makinen. 1988. Soluble 34K binding protein inhibits the binding of insulin-like growth factor I to its cell receptors in human secretory phase endometrium: evidence for autocrine/paracrine regulation of growth factor action. J. Clin. Endocrinol. Metab. 66:173-180.
  53. Schoen, T. J., D. C. Beebe, D. R. Clemmons, G. L. Chader and R. J. Waldbillig. 1992. Local synthesis and developmental regulation of avian vitreal insulin-like growth factor-binding proteins: A model for independent regulation in extravascular and vascular compartments. Endocrinol. 131:2846-2854.
  54. Schoen, T. J., K. Mazuruk, R. J. Waldbilling, J. Potts, D. C. Beebe, G. J. Chader and I. R. Rodriguez. 1995. Cloning and characterization of a chick embryo cDNA and gene for IGF binding protein-2. J. Mol. Endocrinol. 15:49-59.
  55. Serrano, J., A. R. Shuldiner, C. R. Roberts, Jr., D. LeRoith and F. De Pablo. 1990. The insulin-like growth factor I (IGF-I) gene is expressed in chick embryos during early organogenesis. Endocrinol. 127:1547-1549.
  56. Shimasaki, S. and N. Ling. 1991. Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6). Prog. Growth Factor Res. 3:243-266.
  57. Straus, D. S. and C. D. Takemoto. 1990. Effect of dietary protein deprivation on insulin-like growth factor (IGF)-I and -II, IGF binding protein-2, and serum albumin gene expression in rat. Endocrinol. 127:1849-1860.
  58. Suwanickul, A., S. L. Morris and D. R. Powell. 1993. Identification of an insulin-responsive element in the promoter of the human gene for insulin-like growth factor binding protein-1. J. Biol. Chem. 268:17063-17068.
  59. Takenaka, A., K. Komori, T. Morishita, S. Takahashi, T. Hidaka and T. Noguchi. 2000a. Amino acid regulation of gene transcription of rat insulin-like growth factor-binding protein-1. J. Endocrinol. 164:R11-16.
  60. Takenaka, A., N. Oki, S. Takahashi and T. Noguchi. 2000b. Dietary restriction of single essential amino acids reduces plasma insulin-like growth factor-I (IGF-I) but does not affect plasma IGF-binding protein-1 in rats. J. Nutr. 130:2910-2914.
  61. Tanaka, M., Y. Hayashida, K. Sakaguchi, T. Ohkubo, M. Wakita, S. Hoshino and K. Nakashima. 1996. Growth hormoneindependent expression of insulin-like growth factor I messenger ribonucleic acid in extrahepatic tissues of the chicken. Endocrinol. 137:30-34.
  62. Upton, F. Z., G. L. Francis, M. Ross, J. C. Wallace and F. J. Ballard. 1992. Production and characterization of recombinant chicken insulin-like growth factor-I from Escherichia coli. J. Mol. Endocrinol. 9:83-92.
  63. Villafuerte, B. C., W. Zhao, A. C. Herington, R. Saffery and L. S. Phillips. 1997. Identification of an insulin-responsive element in the rat insulin-like growth factor-binding protein-3 gene. J. Biol. Chem. 272:5024-5030.
  64. Xu, X., S. A. Bennett, R. L. Ingram and W. E. Sonntag. 1995. Decreases in growth hormone receptor signal transduction contribute to the decline in insulin-like growth factor I gene expression with age. Endocrinol. 136:4551-4557.

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