Expression Profiles of the Insulin-like Growth Factor System Components in Liver Tissue during Embryonic and Postnatal Growth of Erhualian and Yorkshire Reciprocal Cross F1 Pigs

  • Pan, Zengxiang (College of Animal Science and Technology, Nanjing Agricultural University) ;
  • Zhang, Junlei (College of Animal Science and Technology, Nanjing Agricultural University) ;
  • Zhang, Jinbi (College of Animal Science and Technology, Nanjing Agricultural University) ;
  • Zhou, Bo (College of Animal Science and Technology, Nanjing Agricultural University) ;
  • Chen, Jie (College of Animal Science and Technology, Nanjing Agricultural University) ;
  • Jiang, Zhihua (Department of Animal Sciences, Washington State University) ;
  • Liu, Honglin (College of Animal Science and Technology, Nanjing Agricultural University)
  • Received : 2011.10.23
  • Accepted : 2012.01.22
  • Published : 2012.07.01


In Erhualian and Yorkshire reciprocal cross $F_1$ pig populations, we examined the mRNA expression characteristic of liver-derived IGF-1, IGF-1R, IGF-2, IGF-2R and IGFBP-3 during the embryonic and postnatal developmental periods (E50, E70, E90, D1, D20, D70, D120 and D180). Our results demonstrated that the IGF-system genes mRNA levels exhibited an ontogenetic expression pattern, which was potentially associated with the porcine embryonic development, postnatal growth, organogenesis and even the initiation and acceleration of puberty. The expression pattern of IGF-system genes showed variation in the reciprocal cross ($F_1$ YE and EY pigs). This study also involved the expression features of imprinted genes IGF-2 and IGF-2R. The parent-of-origin effect of imprinted genes was reflected by their differential expression between the reciprocal crosses populations. The correlation analysis also indicated that the regulatory network and mechanisms involved in the IGF system were a complex issue that needs to be more fully explored. A better understanding of IGF system components and their interactive mechanisms will enable researchers to gain insights not only into animal organogenesis but also into somatic growth development and even reproduction.


Supported by : Natural Science Foundation of Jiangsu Province


  1. Adams, T., V. Epa, T. Garrett and C. Ward. 2000. Structure and function of the type 1 insulin-like growth factor receptor. Cell. Mol. Life Sci. 57:1050-1093.
  2. Annunziata, M., R. Granata and E. Ghigo. 2011. The IGF system. Acta Diabetol. 48:1-9.
  3. Argente, J., V. Barrios, J. Pozo, M. Munoz, F. Hervas, M. Stene and M. Hernandez. 1993. Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age-and sex-related changes. J. Clin. Endocrinol. Metab. 77:1522-1528.
  4. 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.
  5. Bale, L. K. and C. A. Conover. 1992. Regulation of insulin-like growth factor binding protein-3 messenger ribonucleic acid expression by insulin-like growth factor I. Endocrinology 131:608-614.
  6. Bischoff, S. R., S. Tsai, N. Hardison, A. A. Motsinger-Reif, B. A. Freking, D. Nonneman, G. Rohrer and J. A. Piedrahita. 2009. Characterization of conserved and nonconserved imprinted genes in swine. Biol. Reprod. 81:906-920.
  7. Cha, B. H., B. K. Kim, S. Hwang, B. C. Yang, G. S. Im, M. R. Park, J. S. Woo, M. J. Kim, H. H. Seong and J. H. Cho. 2010. Imprinted gene mRNA expression during porcine peri-implantation development. Asian-Aust. J. Anim. Sci. 23:693-699.
  8. Chaillet, J. R. 1994. Genomic imprinting: lessons from mouse transgenes. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 307:441-449.
  9. Cheng, R., K. M. Chang and J. L. Wu. 2002. Different temporal expressions of Tilapia (oreochromis mossambicus) insulin-like growth factor-I and IGF binding protein-3 after growth hormone induction. Mar. Biotechnol. 4:218-225.
  10. Christoforidis, A., I. Maniadaki and R. Stanhope. 2005. Growth hormone/insulin-like growth factor-1 axis during puberty. Pediatr. Endocrinol. Rev. 3:5-10.
  11. Clemmons, D. R. 1997. Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev. 8:45-62.
  12. Collett-Solberg, P. and P. Cohen. 2000. Genetics, chemistry, and function of the IGF/IGFBP system. Endocrine 12:121-136.
  13. Curley, J. P. and E. B. Keverne. 2004. Imprinting and behavior. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. John Wiley & Sons, Ltd.
  14. De Pablo, F., H. L. Robcis, T. Caldes, J. Alemany, L. Scavo and J. Serrano. 1991. Insulin-like growth factor-I and insulin as growth and differentiation factors in chicken embryogenesis. Poult. Sci. 70:1790-1796.
  15. DeChiara, T. M., A. Efstratiadis and E. J. Robertsen. 1990. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 345:78-80.
  16. Desbois-Mouthon, C., D. Wendum, A. Cadoret, C. Rey, P. Leneuve, A. Blaise, C. Housset, F. Tronche, Y. Le Bouc and M. Holzenberger. 2006. Hepatocyte proliferation during liver regeneration is impaired in mice with liver-specific IGF-1R knockout. FASEB J. 20:773-775.
  17. Eigenmann, J. E., A. Amador and D. F. Patterson. 1988. Insulin-like growth factor I levels in proportionate dogs, chondrodystrophic dogs and in giant dogs. Acta Endocrinol. (Copenh.) 118:105-108.
  18. Froesch, E., C. Schmid, J. Schwander and J. Zapf. 1985. Actions of insulin-like growth factors. Annu. Rev. Physiol. 47:443-467.
  19. Gerrard, D., C. Okamura, M. Ranalletta and A. Grant. 1998. Developmental expression and location of IGF-I and IGF-II mRNA and protein in skeletal muscle. J. Anim. Sci. 76:1004-1011.
  20. Haig, D. 2004. Genomic imprinting and kinship: how good is the evidence? Annu. Rev. Genet. 38:553-585.
  21. Haig, D. and C. Graham. 1991. Genomic imprinting and the strange case of the insulin-like growth factor II receptor. Cell 64:1045-1046.
  22. Heyner, S., M. Farber and I. Rosenblum. 1990. The insulin family of peptides in early mammalian development. Curr. Top. Dev. Biol. 24:137-159.
  23. Hiney, J. K., S. Ojeda and W. L. Dees. 1991. Insulin-like growth factor I: a possible metabolic signal involved in the regulation of female puberty. Neuroendocrinology 54:420-423.
  24. Jorgensen, H. L. 2003. Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Ugeskr L Ger. 165:3429.
  25. Jones, J. I. and D. R. Clemmons. 1995. Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. 16:3-34.
  26. Killian, J. K., J. C. Byrd, J. V. Jirtle, B. L. Munday, M. K. Stoskopf, R. G. MacDonald and R. L. Jirtle. 2000. M6P/IGF2R imprinting evolution in mammals. Mol. Cell 5:707-716.
  27. Killian, J. K., C. M. Nolan, A. A. Wylie, T. Li, T. H. Vu, A. R. Hoffman and R. L. Jirtle. 2001. Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary. Hum. Mol. Genet. 10:1721-1728.
  28. Krassas, G., N. Pontikides, T. Kaltsas, A. Dumas, J. Frystyk, J. Chen and A. Flyvbjerg. 2003. Free and total insulin-like growth factor (IGF)-I,-II, and IGF binding protein-1,-2, and-3 serum levels in patients with active thyroid eye disease. J. Clin. Endocrinol. Metab. 88:132-135.
  29. Lackey, B. R., S. L. Gray and D. M. Henricks. 1999. The insulin-like growth factor (IGF) system and gonadotropin regulation: actions and interactions. Cytokine Growth Factor Rev. 10:201-217.
  30. Laron, Z. and B. Klinger. 1998. Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance). Eur. J. Endocrinol. 138:176-180.
  31. Lau, M., C. Stewart, Z. Liu, H. Bhatt, P. Rotwein and C. L. Stewart. 1994. Loss of the imprinted IGF2/cation-independent mannose 6-phosphate receptor results in fetal overgrowth and perinatal lethality. Genes Dev. 8:2953-2963.
  32. Le Roith, D., C. Bondy, S. Yakar, J. L. Liu and A. Butler. 2001. The somatomedin hypothesis: 2001. Endocr. Rev. 22:53-74.
  33. LeRoith, D. 2008. Clinical relevance of systemic and local IGF-I: lessons from animal models. Pediatr. Endocrinol. Rev. 5:739-743.
  34. Levitt Katz, L. E., R. G. Rosenfeld and S. P. Cohen. 1995. Clinical significance of insulin-like growth factor binding proteins (IGFBPs). Endocrinologist 5:36-43.
  35. Li, C., Y. Bin, C. Curchoe, L. Yang, D. Feng, Q. Jiang, X. C. Tian and S. Zhang. 2008. Genetic imprinting of H19 and IGF2 in domestic pigs (Sus scrofa). Anim. Biotechnol. 19:22-27.
  36. Li, F., R. Zhao, Q. Xu, W. Chen, Y. Ma and J. Chen. 2003. Characteristics of testosterone secretion in male Erhualian and Large White pigs in different developmental stages. J. Nanjing Agricultural University 26:117-119.
  37. Li, S., S. Yakar and P. Brodt. 2011. Role of the IGF-axis in liver metastasis: experimental and clinical evidence (Ed. P. Brodt). Liver metastasis: biology and clinical management. Springer Netherlands, 233-271.
  38. Lighten, A. D., K. Hardy, R. M. L. Winston and G. E. Moore. 1997. IGF2 is parentally imprinted in human preimplantation embryos. Nat. Genet. 15:122-123.
  39. Liu, J. L., A. Grinberg, H. Westphal, B. Sauer, D. Accili, M. Karas and D. LeRoith. 1998. Insulin-like growth factor-I affects perinatal lethality and postnatal development in a gene dosage-dependent manner: manipulation using the Cre/loxP system in transgenic mice. Mol. Endocrinol. 12:1452-1462.
  40. 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.
  41. Lu, F., Z. Jiang, X. Wang, Y. Luo, X. Li and H. Liu. 2010. Role of the insulin-like growth factor system in epiphyseal cartilage on the development of Langshan and Arbor Acres chickens, Gallus domesticus. Poult. Sci. 89:956-965.
  42. Lu, F., X. Wang, Q. Pan, R. Huang and H. Liu. 2008. Expression of genes involved in the somatotropic, thyrotropic, and corticotropic axes during development of Langshan and Arbor Acres chickens. Poult. Sci. 87:2087-2097.
  43. Moses, A. C., P. S. Nissley, J. Passamani and R. M. White. 1979. Further characterization of growth hormone-dependent somatomedin-binding proteins in rat serum and demonstration of somatomedin-binding proteins produced by rat liver cells in culture. Endocrinology 104:536-546.
  44. Moses, A. C., S. P. Nissley, P. A. Short, M. M. Rechler, R. M. White, A. B. Knight and O. Z. Higa. 1980. Increased levels of multiplication-stimulating activity, an insulin-like growth factor, in fetal rat serum. Proc. Natl. Acad. Sci. USA 77:3649-3653.
  45. Nezer, C., L. Moreau, B. Brouwers, W. Coppieters, J. Detilleux, R. Hanset, L. Karim, A. Kvasz, P. Leroy and M. Georges. 1999. An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs. Nat. Genet. 21:155-156.
  46. Ohlsson, C., S. Mohan, K. Sjogren, Tivesten, J. Isgaard, O. Isaksson, J. O. Jansson and J. Svensson. 2009. The role of liver-derived insulin-like growth factor-I. Endocr. Rev. 30:494-535.
  47. Pavelic, J., B. Radakovic and K. Pavelic. 2007. Insulin-like growth factor 2 and its receptors (IGF 1R and IGF 2R/mannose 6-phosphate) in endometrial adenocarcinoma. Gynecol. Oncol. 105:727-735.
  48. Powell-Braxton, L., P. Hollingshead, C. Warburton, M. Dowd, S. Pitts-Meek, D. Dalton, N. Gillett and T. A. Stewart. 1993. IGF-I is required for normal embryonic growth in mice. Genes Dev. 7:2609-2617.
  49. Rabnott, G., P. Kaye, M. Pantaleon and H. ericho. 2003. The role of insulin-like growth factor II and its receptor in mouse preimplantation development. Reprod. Fertil. Dev. 15:37-45.
  50. Rajaram, S., D. J. Baylink and S. Mohan. 1997. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr. Rev. 18:801-831.
  51. Rappolee, D. A., K. S. Sturm, O. Behrendtsen, G. A. Schultz, R. A. Pedersen and Z. Werb. 1992. Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Genes Dev. 6:939-952.
  52. Ruan, W., L. Powell-Braxton, J. J. Kopchick and D. L. Kleinberg. 1999. Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development. Endocrinology 140:1984-1989.
  53. Ryan, P. D. and P. E. Goss. 2008. The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist 13:16-24.
  54. Sachdev, D. and D. Yee. 2001. The IGF system and breast cancer. Endocr. Relat. Cancer 8:197-209.
  55. Sjogren, K., J. L. Liu, K. Blad, S. Skrtic, O. Vidal, V. Wallenius, D. LeRoith, J. T rnell, O. G. P. Isaksson and J. O. Jansson. 1999. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc. Natl. Acad. Sci. USA 96:7088-7092.
  56. Skalkidou, A., E. Petridou, E. Papathoma, H. Salvanos, S. Kedikoglou, G. Chrousos and D. Trichopoulos. 2003. Determinants and consequences of major insulin-like growth factor components among full-term healthy neonates. Cancer Epidemiol. Biomarkers Prev. 12:860-865.
  57. Stratikopoulos, E., M. Szabolcs, I. Dragatsis, A. Klinakis and A. Efstratiadis. 2008. The hormonal action of IGF1 in postnatal mouse growth. Proc. Natl. Acad. Sci. USA 105:19378-19383.
  58. Tannenbaum, G., H. J. Guyda and B. I. Posner. 1983. Insulin-like growth factors: a role in growth hormone negative feedback and body weight regulation via brain. Science 220:77-79.
  59. Tryfonidou, M., M. Holl, M. Vastenburg, M. Oosterlaken-Dijksterhuis, D. Birkenh ger-Frenkel, W. Van den Brom and H. Hazewinkel. 2003. Hormonal regulation of calcium homeostasis in two breeds of dogs during growth at different rates. J. Anim. Sci. 81:1568-1580.
  60. Uchijima, Y., A. Takenaka, S. I. Takahashi and T. Noguchi. 1995. Production of insulin-like growth factors and their binding proteins in primary cultures of rat liver parenchymal and nonparenchymal cells. Biosci. Biotechnol. Biochem. 59:1503-1515.
  61. Velloso, C. P. 2008. Regulation of muscle mass by growth hormone and IGF-I. Br. J. Pharmacol. 154:557-568.
  62. Wang, Z. Q., M. R. Fung, D. P. Barlow and E. F. Wagner. 1994. Regulation of embryonic growth and lysosomal targeting by the imprintedIGF2/Mpr gene. Nature 372:464-467.
  63. Wittkopp, P. J., B. K. Haerum and A. G. Clark. 2006. Parent-of-Origin effects on mRNA expression in drosophila melanogaster not caused by genomic imprinting. Genetics 173:1817-1821.
  64. Yakar, S., J. L. Liu, B. Stannard, A. Butler, D. Accili, B. Sauer and D. LeRoith. 1999. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc. Natl. Acad. Sci. USA 96:7324-7329.

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