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Effects of l-arginine on growth hormone and insulin-like growth factor 1

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Abstract

l-Arginine has been reported to promote cellular and organismal growth. In this study, the effects of l-arginine on the expression of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), the two key growth factors, are investigated in cultured GH3 pituitary epithelium and HepG2 cells, respectively. l-Arginine significantly induced the gene expression of GH and IGF-1 in GH3 pituitary epithelium and HepG2 hepatocytes respectively, and reduced IGF binding protein-1 gene expression in HepG2 cells assessed via quantitative polymerase chain reaction analysis. l-Arginine also significantly induced GH and IGF-1 hormone secretion from GH3 and HepG2 cells, respectively. In addition, the multi-target ELISA analysis conducted revealed that phosphorylation of p-38 MAPK, MEK, and JNK were significantly increased in HepG2 cells, suggesting l-arginine-induced activation of the MAPK signaling pathway. These results suggest that l-arginine promotes the synthesis and secretion of GH and IGF-1 in vitro and induces the MAPK signaling cascade in cultured hepatocytes.

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References

  1. Root AW. Neurophysiological regulation of the secretion of growth hormone. J. Endocrinol. Invest. 12: 3–7 (1989).

    CAS  Google Scholar 

  2. Ross RJ. GH, IGF-I and binding proteins in altered nutritional states. Int. J. Obes. Relat. Metab. Disord. 24 Suppl 2: S92–95 (2000).

    Article  CAS  Google Scholar 

  3. Yamauchi T, Ueki K, Tobe K, Tamemoto H, Sekine N, Wada M, Honjo M, Takahashi M, Takahashi T, Hirai H, Tsushima T, Akanuma Y, Fujita T, Komuro I, Yazaki Y, Kadowaki T. Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase activation and gene expression. Endocr. J. 45: S27–31 (1998).

    Article  CAS  Google Scholar 

  4. Nilsson A, Ohlsson C, Isaksson OG, Lindahl A, Isgaard J. Hormonal regulation of longitudinal bone growth. Eur. J. Clin. Nutr. 48: 150–160 (1994).

    Google Scholar 

  5. Butler AA, LeRoith D. Minireview: tissue-specific versus generalized gene targeting of the igf1 and igf1r genes and their roles in insulin-like growth factor physiology. Endocrinology 142: 1685–1688 (2001).

    Article  CAS  Google Scholar 

  6. Kelley KM, Oh Y, Gargosky SE, Gucev Z, Matsumoto T, Hwa V, Ng L, Simpson DM, Rosenfeld RG. Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int. J. Biochem. Cell Biol. 28: 619–637 (1996).

    Article  CAS  Google Scholar 

  7. Levine AJ, Feng Z, Mak TW, You H, Jin S. Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev. 20: 267–275 (2006).

    Article  CAS  Google Scholar 

  8. Werner H, Le Roith D. The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. Crit. Rev. Oncog. 8: 71–92 (1997).

    Article  CAS  Google Scholar 

  9. Lagarrigue S, Heberden C, Martel P, Gaillard-Sanchez I. The transformation of c-jun-overexpressing cells is correlated with IGFS-induced c-jun phosphorylation. Biochem. Biophys. Res. Commun. 217: 501–508 (1995).

    Article  CAS  Google Scholar 

  10. Ong J, Yamashita S, Melmed S. Insulin-like growth factor I induces c-fos messenger ribonucleic acid in L6 rat skeletal muscle cells. Endocrinology 120: 353–357 (1987).

    Article  CAS  Google Scholar 

  11. Delahunty KM, Shultz KL, Gronowicz GA, Koczon-Jaremko B, Adamo ML, Horton LG, Lorenzo J, Donahue LR, Ackert-Bicknell C, Kream BE, Beamer WG, Rosen CJ. Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-I and bone acquisition. Endocrinology 147: 3915–3923 (2006).

    Article  CAS  Google Scholar 

  12. Murphy LJ, Bell GI, Friesen HG. Growth hormone stimulates sequential induction of c-myc and insulin-like growth factor I expression in vivo. Endocrinology 120: 1806–1812 (1987).

    Article  CAS  Google Scholar 

  13. Adriao M, Chrisman CJ, Bielavsky M, Olinto SC, Shiraishi EM, Nunes MT. Arginine increases growth hormone gene expression in rat pituitary and GH3 cells. Neuroendocrinology 79: 26–33 (2004).

    Article  CAS  Google Scholar 

  14. Kong X, Tan B, Yin Y, Gao H, Li X, Jaeger LA, Bazer FW, Wu G. l-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells. J. Nutr. Biochem. 23: 1178–1183 (2012).

    Article  CAS  Google Scholar 

  15. Yao K, Yin YL, Chu W, Liu Z, Deng D, Li T, Huang R, Zhang J, Tan B, Wang W, Wu G. Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J. Nutr. 138: 867–872 (2008).

    CAS  Google Scholar 

  16. Jia Y, Kim JY, Jun HJ, Kim SJ, Lee JH, Hoang MH, Hwang KY, Um SJ, Chang HI, Lee SJ. The natural carotenoid astaxanthin, a PPAR-alpha agonist and PPAR-gamma antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes. Mol. Nutr. Food Res. 56: 878–888 (2012).

    Article  CAS  Google Scholar 

  17. Bakker NE, Kuppens RJ, Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, Bindels-de Heus GC, Bocca G, Haring DA, Hoorweg-Nijman JJ, Houdijk EC, Jira PE, Lunshof L, Odink RJ, Oostdijk W, Rotteveel J, Van Alfen AA, Van Leeuwen M, Van Wieringen H, Wegdam-den Boer ME, Zwaveling-Soonawala N, Hokken-Koelega AC. Bone mineral density in children and adolescents with prader-willi syndrome: a longitudinal study during puberty and 9 years of growth hormone treatment. J. Clin. Endocrinol. Metab. 100: 1609–1618 (2015).

    Article  CAS  Google Scholar 

  18. Gourmelen M, Le Bouc Y, Girard F, Binoux M. Serum levels of insulin-like growth factor (IGF) and IGF binding protein in constitutionally tall children and adolescents. J. Clin. Endocrinol. Metab. 59: 1197–1203 (1984).

    Article  CAS  Google Scholar 

  19. Rubeck KZ, Bertelsen S, Vestergaard P, Jorgensen JO. Impact of GH substitution on exercise capacity and muscle strength in GH-deficient adults: a meta-analysis of blinded, placebo-controlled trials. Clin. Endocrinol. (Oxf). 71: 860–866 (2009).

    Article  CAS  Google Scholar 

  20. Widdowson WM, Gibney J. The effect of growth hormone (GH) replacement on muscle strength in patients with GH-deficiency: a meta-analysis. Clin. Endocrinol. (Oxf). 72: 787–792 (2010).

    Article  CAS  Google Scholar 

  21. Brown-Borg HM, Bartke A. GH and IGF1: roles in energy metabolism of long-living GH mutant mice. J. Gerontol. A Biol. Sci. Med. Sci. 67: 652–660 (2012).

    Article  Google Scholar 

  22. Samra JS, Clark ML, Humphreys SM, MacDonald IA, Bannister PA, Matthews DR, Frayn KN. Suppression of the nocturnal rise in growth hormone reduces subsequent lipolysis in subcutaneous adipose tissue. Eur. J. Clin. Invest. 29: 1045–1052 (1999).

    Article  CAS  Google Scholar 

  23. Lanning NJ, Carter-Su C. Recent advances in growth hormone signaling. Rev. Endocr. Metab. Disord. 7: 225–235 (2006).

    Article  CAS  Google Scholar 

  24. Herrington J, Smit LS, Schwartz J, Carter-Su C. The role of STAT proteins in growth hormone signaling. Oncogene 19: 2585–2597 (2000).

    Article  CAS  Google Scholar 

  25. Feng Z, Levine AJ. The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein. Trends Cell Biol. 20: 427–434 (2010).

    Article  CAS  Google Scholar 

  26. Boger RH. The pharmacodynamics of l-arginine. Altern. Ther. Health Med. 20: 48–54 (2014).

    Google Scholar 

  27. Chausse AA, Nivet-Antoine V, Martin C, Clot JP, Galen FX. Protective effect of nitric oxide on isolated rat hepatocytes submitted to an oxidative stress. Metabolism 51: 175–179 (2002).

  28. Luscher TF. Endothelium-derived nitric oxide: the endogenous nitrovasodilator in the human cardiovascular system. Eur. Heart J. 12 Suppl E: 2–11 (1991).

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. NRF-2016R1A2A2A05005483).

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Sciences and Biotechnology for BK21 PLUS, Korea University, Seoul, 02841, Korea

    Hyun-Seok Oh, Chunyan Wu & Sung-Joon Lee

  2. Rice Research Division, National Institute of Crop Science, Rural Development Administration, Suwon, 441-857, Korea

    Se Kwan Oh & Jum Seek Lee

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Correspondence to Sung-Joon Lee.

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Oh, HS., Oh, S.K., Lee, J.S. et al. Effects of l-arginine on growth hormone and insulin-like growth factor 1. Food Sci Biotechnol 26, 1749–1754 (2017). https://doi.org/10.1007/s10068-017-0236-6

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