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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Root AW. Neurophysiological regulation of the secretion of growth hormone. J. Endocrinol. Invest. 12: 3–7 (1989).
Ross RJ. GH, IGF-I and binding proteins in altered nutritional states. Int. J. Obes. Relat. Metab. Disord. 24 Suppl 2: S92–95 (2000).
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).
Nilsson A, Ohlsson C, Isaksson OG, Lindahl A, Isgaard J. Hormonal regulation of longitudinal bone growth. Eur. J. Clin. Nutr. 48: 150–160 (1994).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Lanning NJ, Carter-Su C. Recent advances in growth hormone signaling. Rev. Endocr. Metab. Disord. 7: 225–235 (2006).
Herrington J, Smit LS, Schwartz J, Carter-Su C. The role of STAT proteins in growth hormone signaling. Oncogene 19: 2585–2597 (2000).
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).
Boger RH. The pharmacodynamics of l-arginine. Altern. Ther. Health Med. 20: 48–54 (2014).
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).
Luscher TF. Endothelium-derived nitric oxide: the endogenous nitrovasodilator in the human cardiovascular system. Eur. Heart J. 12 Suppl E: 2–11 (1991).
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. NRF-2016R1A2A2A05005483).
Conflict of interest
The authors declare that there is no conflict of interest.
About this article
Cite this article
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
- Growth hormone
- Insulin-like growth factor 1
- Mitogen-activated protein kinase