Modulation of the Somatotropic Axis in Periparturient Dairy Cows

  • Kim, Jin Wook (Department of Animal Bioscience (Insti. of Agric. and Life Sci.), Gyeongsang National University)
  • Received : 2013.03.05
  • Accepted : 2013.10.27
  • Published : 2014.01.01


This review focuses on modulation of growth hormone (GH) and its downstream actions on periparturient dairy cows undergoing physiological and metabolic adaptations. During the periparturient period, cows experience a negative energy balance implicating that the feed intake does not meet the total energy demand for the onset of lactation. To regulate this metabolic condition, key hormones of somatotropic axis such as GH, IGF-I and insulin must coordinate adaptations required for the preservation of metabolic homeostasis. The hepatic GHR1A transcript and GHR protein are reduced at parturition, but recovers on postpartum. However, plasma IGF-I concentration remains low even though hepatic abundance of the GHR and IGF-I mRNA return to pre-calving value. This might be caused by alternation in IGFBPs and ALS genes, which consequently affect the plasma IGF-I stability. Plasma insulin level declines in a parallel manner with the decrease in plasma IGF-I after parturition. Increased GH stimulates the lipolytic effects and hepatic glucose synthesis to meet the energy requirement for mammary lactose synthesis, suggesting that GH antagonizes insulin-dependent glucose uptake and attenuates insulin action to decrease gluconeogenesis.


  1. Bauman, D. E. 1999. Bovine somatotropin and lactation: from basic science to commercial application. Domest. Anim. Endocrinol. 17:101-116.
  2. Bauman, D. E. 2000. Ruminant Physiology digestion, metabolism, growth and reproduction. CABI Publishing, New York. 18:331.
  3. Bauman, D. E. and R. G. Vernon. 1993. Effects of exogenous bovine somatotropin on lactation. Annu. Rev. Nutr. 13:437-461.
  4. Baxter, R. C. 1988. Characterization of the acid-labile subunit of the growth hormone-dependent insulin-like growth factor binding protein complex. J. Clin. Endocrinol. Metab. 67:265-272.
  5. Baxter, R. C. and J. L. Martin. 1989. Structure of the Mr 140,000 growth hormone-dependent insulin-like growth factor binding protein complex: determination by reconstitution and affinity-labeling. Proc. Natl. Acad. Sci. USA 86:6898-6902.
  6. Baxter, R. C., J. L. Martin, and V. A. Beniac. 1989. High molecular weight insulin-like growth factor binding protein complex. Purification and properties of the acid-labile subunit from human serum. J. Biol. Chem. 264:11843-11848.
  7. Bell, A. W. 1995. Regulation of organic nutrient metabolism during transition from late pregnancy to early lactation. J. Anim. Sci. 73:2804-2819.
  8. Binoux, M. and P. Hossenlopp. 1988. Insulin-like growth factor (IGF) and IGF-binding proteins: comparison of human serum and lymph. J. Clin. Endocrinol. Metab. 67:509-514.
  9. Boisclair, Y. R., D. Seto, S. Hsieh, K. R. Hurst, and G. T. Ooi. 1996. Organization and chromosomal localization of the gene encoding the mouse acid labile subunit of the insulin-like growth factor binding complex. Proc. Natl. Acad. Sci. USA 93:10028-10033.
  10. Bowers, C. Y. 1998. Growth hormone-releasing peptide (GHRP). Cell. Mol. Life Sci. 54:1316-1329.
  11. Brazeau, P., W. Vale, R Burgus, N. Ling, M. Butcher, J. Rivier, and R. Guillemin. 1973. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77-79.
  12. Butler, J. H. and P. D. Gluckman. 1986. Circulating insulin-like growth factor-binding proteins in fetal, neonatal and adult sheep. J. Endocrinol. 109:333-338.
  13. Butler, S. T., A. L. Marr, S. H. Pelton, R. P. Radcliff, M. C. Lucy, and W. R. Butler. 2003. Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A. J. Endocrinol. 176: 205-217.
  14. Cohick, W. S., M. A. McGuire, D. R. Clemmons, and D. E. Bauman. 1992. Regulation of insulin-like growth factor-binding proteins in serum and lymph of lactating cows by somatotropin. Endocrinology 130:1508-1514.
  15. Dai, J. and R. C. Baxter. 1992. Molecular cloning of the acid-labile subunit of the rat insulin-like growth factor binding protein complex. Biochem. Biophys. Res. Commun.188:304-309.
  16. Daughaday, W. H. and P. Rotwein. 1989. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr. Rev. 10:68-91.
  17. Davey, H. W., T. Xie, M. J. McLachlan, R. J. Wilkins, D. J. Waxman, and D. R. Grattan. 2001. STAT5b is required for GH-induced liver IGF-I gene expression. Endocrinology 142:3836-3841.
  18. Edens, A. and F. Talamantes. 1998. Alternative processing of growth hormone receptor transcripts. Endocr. Rev. 19:559-582.
  19. Etherton, T. D. and D. E. Bauman. 1998. Biology of somatotropin in growth and lactation of domestic animals. Physiol. Rev. 78:745-761.
  20. Firth, S. M. and R. C. Baxter. 2002. Cellular actions of the insulin-like growth factor binding proteins. Endocr. Rev. 23:824-854.
  21. Firth, S. M., U. Ganeshprasad, and R. C. Baxter. 1998. Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3. J. Biol. Chem. 273:2631-2638.
  22. Gatford, K. L., A. R. Egan, I. J. Clarke, and P. C. Owens. 1998. Sexual dimorphism of the somatotrophic axis. J. Endocrinol. 157:373-389.
  23. Hayirli, A. 2006. The role of exogenous insulin in the complex of hepatic lipidosis and ketosis associated with insulin resistance phenomenon in postpartum dairy cattle. Vet. Res. Commun. 30:749-774.
  24. Heap, D., R. J. Collier, C. K. Boyd, and M. C. Lucy. 1996. Expression of alternate growth hormone receptor messenger RNA in ovary and uterus of cattle. Domest. Anim. Endocrinol. 13:421-430.
  25. Heap, D., M. C. Lucy, R. J. Collier, C. K. Boyd, and W. C. Warren. 1995. Rapid communication: nucleotide sequence of the promoter and first exon of the somatotropin receptor gene in cattle. J. Anim. Sci. 73:1529.
  26. Herrington, J. and C. Carter-Su. 2001. Signaling pathways activated by the growth hormone receptor. Trends Endocrinol. Metab. 12:252-257.
  27. Houseknecht, K. L., D. A. Dwyer, D. P. Lanna, and D. E. Bauman. 1995. Effect of somatotropin on adipose tissue metabolism: ontogeny of the enhanced response to adrenergic challenge in the lactating cow. Domest. Anim. Endocrinol. 12:105-113.
  28. Janosi, J. B., P. A. Ramsland, M. R. Mott, S. M. Firth, R. C. Baxter, and P. J. Delhanty. 1999. The acid-labile subunit of the serum insulin-like growth factor-binding protein complexes. Structural determination by molecular modeling and electron microscopy. J. Biol. Chem. 274:23328-23332.
  29. Jiang, H. and M. C. Lucy. 2001a. Involvement of hepatocyte nuclear factor-4 in the expression of the growth hormone receptor 1A messenger ribonucleic acid in bovine liver. Mol. Endocrinol. 15:1023-1034.
  30. Jiang, H. and M. C. Lucy. 2001b. Variants of the 5'-untranslated region of the bovine growth hormone receptor mRNA: isolation, expression and effects on translational efficiency. Gene 265:45-53.
  31. Jiang, H., C. S. Okamura, and M. C. Lucy. 1999. Isolation and characterization of a novel promoter for the bovine growth hormone receptor gene. J. Biol. Chem. 274:7893-7900.
  32. Jiang, H., C. S. Okamura, C. K. Boyd, and M. C. Lucy. 2000. Identification of Sp1 as the transcription factor for the alternative promoter P2 of the bovine growth hormone receptor gene. J. Mol. Endocrinol. 24:203-214.
  33. Jiang, H., Y. Wang, M. Wu, Z. Gu, S. J. Frank, and R. Torres-Diaz. 2007. Growth hormone stimulates hepatic expression of bovine growth hormone receptor mRNA through STAT-activation of a major growth hormone receptor gene promoter. Endocrinology 148:3307-3315.
  34. Jones, J. I. and D. R. Clemmons. 1995. Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. 16: 3-34.
  35. Kim, J. W., R. P. Rhoads, S. S. Block, T. R. Overton, S. J. Frank, and Y. R. Boisclair. 2004. Dairy cows experience selective reduction of the hepatic growth hormone receptor during the periparturient period. J. Endocrinol. 181:281-290.
  36. Kim, J. W., R. P. Rhoads, N. Segoale, N. B. Kristensen, D. E. Bauman, and Y. R. Boisclair. 2006. Isolation of the cDNA encoding the acid labile subunit (ALS) of the 150 kDa IGF-binding protein complex in cattle and ALS regulation during the transition from pregnancy to lactation. J. Endocrinol. 189:583-593.
  37. Kim, J. W. and Y. R. Boislciar. 2008. Growth hormone signaling in the regulation of acid laile subunit. Asian-Aust. J. Anim. Sci. 21:754-768.
  38. Knapp, J. R., H. C. Freetly, B. L. Reis, C. C. Calvert, and R. L. Baldwin. 1992. Effects of somatotropin and substrates on patterns of liver metabolism in lactating dairy cattle. J. Dairy Sci. 75:1025-1035.
  39. Kobayashi, Y., C. K. Boyd, C. J. Bracken, W. R. Lamberson, D. H. Keisler, and M. C. Lucy. 1999. Reduced growth hormone receptor (GHR) messenger ribonucleic acid in liver of periparturient cattle is caused by a specific down-regulation of GHR 1A that is associated with decreased insulin-like growth factor I. Endocrinology 140:3947-3954.
  40. Kojima, M., H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, and K. Kangawa. 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660.
  41. Kopchick, J. J. and J. M. Andry. 2000. Growth hormone (GH), GH receptor, and signal transduction. Mol. Genet. Metab. 71:293-314.
  42. Le Roith, D., C. Bondy, S. Yakar, J. L. Liu, and A. Butler. 2001. The somatomedin hypothesis: 2001. Endocr. Rev. 22:53-74.
  43. Lee, C. Y., I. Kwak, C. S. Chung, W. S. Choi, R. C. Simmen, and F. A. Simmen. 2001. Molecular cloning of the porcine acid-labile subunit (ALS) of the insulin-like growth factor-binding protein complex and detection of ALS gene expression in hepatic and non-hepatic tissues. J. Mol. Endocrinol. 26:135-144.
  44. Leong, S. R., R. C. Baxter, T. Camerato, J. Dai, and W. I. Wood. 1992. Structure and functional expression of the acid-labile subunit of the insulin-like growth factor-binding protein complex. Mol. Endocrinol. 6:870-876.
  45. Lucy, M. C., H. Jiang, and Y. Kobayashi. 2001. Changes in the somatotrophic axis associated with the initiation of lactation. J. Dairy Sci. 84(E. Suppl.):E113-E119 [The paper is available at]
  46. Lupu, F., J. D. Terwilliger, K. Lee, G. V. Segre, and A. Efstratiadis. 2001. Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev. Biol. 229:141-162.
  47. Mayo, K. E. 1992. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol. Endocrinol. 6:1734-1744.
  48. McGuire, M. A., J. L. Vicini, D. E. Bauman, and J. J. Veenhuizen. 1992. Insulin-like growth factors and binding proteins in ruminants and their nutritional regulation. J. Anim. Sci. 70: 2901-2910.
  49. Mullen, M. P., C. O. Lynch, S. M. Waters, D. J. Howard, P. O. Boyle, D. A. Kenny, F. Buckley, B. Horan, and M. G. Diskin. 2011. Single nucleotide polymorphisms in the growth hormone and insulin-like growth factor-1 genes are associated with milk production, body condition score and fertility traits in dairy cows. Gen. Mol. Res. 10:1819-1830.
  50. Ooi, G. T. and Y. R. Boisclair. 1999. Molecular biology of the IGF binding proteins. In: Rosenfeld, R. and C. Roberts Jr. (eds.), Contemporary Endocrinology: The IGF system. Humans Press, Inc., Totowa, NJ. pp 111-139.
  51. Ooi, G. T., K. R. Hurst, M. N. Poy, M. M. Rechler, and Y. R. Boisclair. 1998. Binding of STAT5a and STAT5b to a single element resembling a gamma- interferon-activated sequence mediates the growth hormone induction of the mouse acid-labile subunit promoter in liver cells. Mol. Endocrinol. 12:675-687.
  52. 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.
  53. Rechler, M. M. 1993. Insulin-like growth factor binding proteins. Vitam. Horm. 47:1-114.
  54. Renaville, R., M. Hammadi, and D. Portetelle. 2002. Role of the somatotropic axis in the mammalian metabolism. Domest. Anim. Endocrinol. 23:351-360.
  55. Rhoads, R. P., J. W. Kim, B. J. Leury, L. H. Baumgard, N. Segoale, S. J. Frank, D. E. Bauman, and Y. R. Boisclair. 2004. Insulin increases the abundance of the growth hormone receptor in liver and adipose tissue of periparturient dairy cows. J. Nutr. 134:1020-1027.
  56. Rhoads, R. P., J. W. Kim, M. E. Van Amburgh, R. A. Ehrhardt, S. J. Frank, and Y. R. Boisclair. 2007. Effect of nutrition on the GH responsiveness of liver and adipose tissue in dairy cows. J. Endocrinol. 195:49-58.
  57. Schwartzbauer, G. and R. K. Menon. 1998. Regulation of growth hormone receptor gene expression. Mol. Genet. Metab. 63:243-253.
  58. Twigg, S. M. and R. C. Baxter. 1998. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J. Biol. Chem. 273:6074-6079.
  59. Twigg, S. M., M. C. Kiefer, J. Zapf, and R. C. Baxter. 1998. Insulin-like growth factor-binding protein 5 complexes with the acid- labile subunit. Role of the carboxyl-terminal domain. J. Biol. Chem. 273:28791-28798.
  60. Ueki, I., G. T. Ooi, M. L. Tremblay, K. R. Hurst, L. A. Bach, and Y. R. Boisclair. 2000. Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system. Proc. Natl. Acad. Sci. USA 97:6868-6873.
  61. Waters, M. J., C. A. Shang, S. N. Behncken, S. P. Tam, H. Li, B. Shen, and P. E. Lobie. 1999. Growth hormone as a cytokine. Clin. Exp. Pharmacol. Physiol. 26:760-764.
  62. Waters, S. M., D. P. Berry, and M. P. Mullen. 2012. Polymorphisms in genes of the somatotrophic axis are independently associated with milk production, udder health, survival and animal size in Holstein-Friesian dairy cattle. J. Anim. Breed. Genet. 129:70-78.
  63. Waters, S. M., M. S. McCabe, D. J. Howard, L. Giblin, D. A. Magee, D. E. MacHugh, and D. P. Berry. 2011. Associations between newly discovered polymorphisms in the Bos taurus growth hormone receptor gene and performance traits in Holstein-Friesian dairy cattle. Anim. Genet. 42:39-49.
  64. Woelfle, J. and P. Rotwein. 2004. In vivo regulation of growth hormone-stimulated gene transcription by STAT5b. Am. J. Physiol. Endocrinol. Metab. 286:E393-401.
  65. Woelfle, J., D. J. Chia, and P. Rotwein. 2003. Mechanisms of growth hormone action: identification of conserved Stat5 binding sites that mediate GH-induced insulin-like growth factor-I gene activation. J. Biol. Chem. 278:51261-51266.
  66. Zapf, J., C. Hauri, M. Waldvogel, and E. R. Froesch. 1986. Acute metabolic effects and half-lives of intravenously administered insulinlike growth factors I and II in normal and hypophysectomized rats. J. Clin. Invest. 77:1768-1775.
  67. Zhu, T., E. L. Goh, R. Graichen, L. Ling, and P. E. Lobie. 2001. Signal transduction via the growth hormone receptor. Cell Signal. 13:599-616.

Cited by

  1. Effects of nutritional status on hormone concentrations of the somatotropin axis and metabolites in plasma and colostrum of Japanese Black cows vol.88, pp.4, 2016,
  2. Increased Concentrations of Insulin-Like Growth Factor Binding Protein (IGFBP)-2, IGFBP-3, and IGFBP-4 Are Associated With Fetal Mortality in Pregnant Cows vol.9, pp.1664-2392, 2018,