Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver

Endocrine Journal

Volumn 59, Issue 11, 2012, Pages 955-962

  Takahashi, Yutaka ^a  

^a KOBE UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Adult growth hormone deficiency (AGHD); Growth hormone (GH); Insulin like growth factor I (IGF I); Nonalcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH)

Indexed keywords

GROWTH HORMONE; SOMATOMEDIN C;

ATHEROSCLEROSIS; CHILD GROWTH; COMORBIDITY; DISEASE COURSE; GROWTH HORMONE DEFICIENCY; HISTOPATHOLOGY; HORMONE SUBSTITUTION; HUMAN; LIVER BIOPSY; LIVER CIRRHOSIS; MORTALITY; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PATHOGENESIS; PREVALENCE; PROTEIN FUNCTION; QUALITY OF LIFE; REVIEW;

ADULT; ANIMALS; FATTY LIVER; HUMAN GROWTH HORMONE; HUMANS; HYPOPITUITARISM; INSULIN-LIKE GROWTH FACTOR I; LIVER; LIVER CIRRHOSIS; MIDDLE AGED; PREVALENCE;

EID: 84871076695     PISSN: 09188959     EISSN: 13484540     Source Type: Journal    
DOI: 10.1507/endocrj.EJ12-0322     Document Type: Review

References (69)

1. Johannsson G, Bengtsson BA (1999) Growth hormone and the metabolic syndrome. J Endocrinol Invest 22: 41-46.
2. Maison P, Balkau B, Souberbielle JC, Cunin P, Vol S, Macquin-Mavier I, Eschwege E (2007) Evidence for distinct effects of GH and IGF-I in the metabolic syndrome. Diabet Med 24: 1012-1018.
3. Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, Bates AS, Stewart PM (2010) Mortality in patients with pituitary disease. Endocr Rev 31: 301-342.
4. Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G (2004) Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab 89: 3306-3312. 20.
5. Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346: 1221-1231.
6. Hashimoto E, Tokushige K (2011) Prevalence, gender, ethnic variations, and prognosis of NASH. J 21. Gastroenterol 46 Suppl 1: 63-69.
7. Adams LA, Talwalkar JA (2006) Diagnostic evaluation of nonalcoholic fatty liver disease. J Clin Gastroenterol 40 Suppl 1: S34-38.
8. Yasui K, Hashimoto E, Tokushige K, Koike K, Shima T, Kanbara Y, Saibara T, Uto H, Takami S, Kawanaka M, Komorizono Y, Okanoue T (2012) Clinical and pathological progression of non-alcoholic steatohepatitis to hepatocellular carcinoma. Hepatol Res 42: 767-773.
9. Adams LA, Angulo P, Lindor KD (2005) Nonalcoholic fatty liver disease. CMAJ 172: 899-905.
10. Rudling M, Norstedt G, Olivecrona H, Reihner E, Gustafsson JA, Angelin B (1992) Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proc Natl Acad Sci U S A 89: 6983-6987.
11. Moller N, Jorgensen JO (2009) Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30: 152-177.
12. Fryburg DA, Barrett EJ (1993) Growth hormone acutely stimulates skeletal muscle but not whole-body protein 25. synthesis in humans. Metabolism 42: 1223-1227.
13. Holt RI, Simpson HL, Sonksen PH (2003) The role of the growth hormone-insulin-like growth factor axis in glucose homeostasis. Diabet Med 20: 3-15.
14. Simpson HL, Jackson NC, Shojaee-Moradie F, Jones RH, Russell-Jones DL, Sonksen PH, Dunger DB, Umpleby AM (2004) Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but 26. no effect on lipid metabolism in type 1 diabetes. J Clin Endocrinol Metab 89: 425-432.
15. Yakar S, Setser J, Zhao H, Stannard B, Haluzik M, Glatt V, Bouxsein ML, Kopchick JJ, LeRoith D (2004) Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. J Clin Invest 27. 113: 96-105.
16. Clemmons DR (2009) Role of IGF-I in skeletal muscle mass maintenance. Trends Endocrinol Metab 20: 349-356. 28.
17. Takano S, Kanzaki S, Sato M, Kubo T, Seino Y (1997) Effect of growth hormone on fatty liver in panhypopituitarism. Arch Dis Child 76: 537-538.
18. Kaji H, Sakurai T, Iguchi G, Murata M, Kishimoto M, Yoshioka S, Iida K, Okimura Y, Chihara K (2002) Adult growth hormone deficiency in Japan: results of investi29. gation by questionnaire. Endocr J 49: 597-604.
19. Ichikawa T, Hamasaki K, Ishikawa H, Ejima E, Eguchi K, Nakao K (2003) Non-alcoholic steatohepatitis and hepatic steatosis in patients with adult onset growth hormone deficiency. Gut 52: 914.
20. Adams LA, Feldstein A, Lindor KD, Angulo P (2004) Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. Hepatology 39: 909-914.
21. Fukuda I, Hizuka N, Yasumoto K, Morita J, Kurimoto M, Takano K (2008) Metabolic co-morbidities revealed in patients with childhood-onset adult GH deficiency after cessation of GH replacement therapy for short stature. Endocr J 55: 977-984.
22. Takahashi Y, Iida K, Takahashi K, Yoshioka S, Fukuoka H, Takeno R, Imanaka M, Nishizawa H, Takahashi M, Seo Y, Hayashi Y, Kondo T, Okimura Y, Kaji H, Kitazawa R, Kitazawa S, Chihara K (2007) Growth hormone reverses nonalcoholic steatohepatitis in a patient with adult growth hormone deficiency. Gastroenterology 132: 938-943.
23. Hong JW, Kim JY, Kim YE, Lee EJ (2011) Metabolic Parameters and Nonalcoholic Fatty Liver Disease in Hypopituitary Men. Horm Metab Res 43: 48-54.
24. Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y, Taura N, Shibata H, Fujimoto M, Toriyama K, Eguchi K (2007) Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int 1: 287-294.
25. Nishizawa H, Iguchi G, Murawaki A, Fukuoka H, Hayashi Y, Kaji H, Yamamoto M, Suda K, Takahashi M, Seo Y, Yano Y, Kitazawa R, Kitazawa S, Koga M, Okimura Y, Chihara K, Takahashi Y (2012) Nonalcoholic fatty liver disease in adult hypopituitary patients with growth hormone deficiency and the impact of growth hormone replacement therapy. Eur J Endocrinol 167: 67-74.
26. Gardner CJ, Irwin AJ, Daousi C, McFarlane IA, Joseph F, Bell JD, Thomas EL, Adams VL, Kemp GJ, Cuthbertson DJ (2012) Hepatic steatosis, GH deficiency and the effects of GH replacement: a Liverpool magnetic resonance spectroscopy study. Eur J Endocrinol 166: 993-1002.
27. Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34: 274-285.
28. Franco C, Brandberg J, Lonn L, Andersson B, Bengtsson BA, Johannsson G (2005) Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebocontrolled trial. J Clin Endocrinol Metab 90: 1466-1474.
29. Donaghy A, Ross R, Wicks C, Hughes SC, Holly J, Gimson A, Williams R (1997) Growth hormone therapy in patients with cirrhosis: a pilot study of efficacy and safety. Gastroenterology 113: 1617-1622.
30. Liu JL, Yakar S, LeRoith D (2000) Conditional knockout of mouse insulin-like growth factor-1 gene using the Cre/loxP system. Proc Soc Exp Biol Med 223: 344-351.
31. Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D (2002) Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 110: 771-781.
32. Yakar S, Liu JL, Stannard B, Butler A, Accili D, Sauer B, LeRoith D (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci U S A 96: 7324-7329.
33. Fan Y, Menon RK, Cohen P, Hwang D, Clemens T, DiGirolamo DJ, Kopchick JJ, Le Roith D, Trucco M, Sperling MA (2009) Liver-specific deletion of the growth hormone receptor reveals essential role of growth hormone signaling in hepatic lipid metabolism. J Biol Chem 284: 19937-19944.
34. Ekberg S, Luther M, Nakamura T, Jansson JO (1992) Growth hormone promotes early initiation of hepatocyte growth factor gene expression in the liver of hypophysectomized rats after partial hepatectomy. J Endocrinol 135: 59-67.
35. Krupczak-Hollis K, Wang X, Dennewitz MB, Costa RH (2003) Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b. Hepatology 38: 1552-1562.
36. Pennisi PA, Kopchick JJ, Thorgeirsson S, LeRoith D, Yakar S (2004) Role of growth hormone (GH) in liver regeneration. Endocrinology 145: 4748-4755.
37. Sos BC, Harris C, Nordstrom SM, Tran JL, Balazs M, Caplazi P, Febbraio M, Applegate MA, Wagner KU, Weiss EJ (2011) Abrogation of growth hormone secretion rescues fatty liver in mice with hepatocyte-specific deletion of JAK2. J Clin Invest 121: 1412-1423.
38. Barclay JL, Nelson CN, Ishikawa M, Murray LA, Kerr LM, McPhee TR, Powell EE, Waters MJ (2011) GH-dependent STAT5 signaling plays an important role in hepatic lipid metabolism. Endocrinology 152: 181-192.
39. Laron Z, Ginsberg S, Webb M (2008) Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion preliminary report. Growth Horm IGF Res 18: 434-438.
40. Donaghy A, Ross R, Gimson A, Hughes SC, Holly J, Williams R (1995) Growth hormone, insulinlike growth factor-1, and insulinlike growth factor binding proteins 1 and 3 in chronic liver disease. Hepatology 21: 680-688.
41. Cuneo RC, Hickman PE, Wallace JD, Teh BT, Ward G, Veldhuis JD, Waters MJ (1995) Altered endogenous growth hormone secretory kinetics and diurnal GH-binding protein profiles in adults with chronic liverdisease. Clin Endocrinol (Oxf) 43: 265-275.
42. Clemmons DR, Klibanski A, Underwood LE, McArthur JW, Ridgway EC, Beitins IZ, Van Wyk JJ (1981) Reduction of plasma immunoreactive somatomedin C during fasting in humans. J Clin Endocrinol Metab 53: 1247-1250.
43. Caro JF, Poulos J, Ittoop O, Pories WJ, Flickinger EG, Sinha MK (1988) Insulin-like growth factor I binding in hepatocytes from human liver, human hepatoma, and normal, regenerating, and fetal rat liver. J Clin Invest 81: 976-981.
44. Stefano JT, Correa-Giannella ML, Ribeiro CM, Alves VA, Massarollo PC, Machado MC, Giannella-Neto D (2006) Increased hepatic expression of insulin-like growth factor-I receptor in chronic hepatitis C. World J Gastroenterol 12: 3821-3828.
45. Kim SO, Park JG, Lee YI (1996) Increased expression of the insulin-like growth factor I (IGF-I) receptor gene in hepatocellular carcinoma cell lines: implications of IGF-I receptor gene activation by hepatitis B virus X gene product. Cancer Res 56: 3831-3836.
46. Tao X, Shen D, Ren H, Zhang X, Zhang D, Ye J, Gu B (2000) Hepatitis B virus X protein activates expression of IGF-IR and VEGF in hepatocellular carcinoma cells. Zhonghua Gan Zang Bing Za Zhi 8: 161-163 (In Chinese).
47. Aleem E, Nehrbass D, Klimek F, Mayer D, Bannasch P (2011) Upregulation of the insulin receptor and type I insulin-like growth factor receptor are early events in hepatocarcinogenesis. Toxicol Pathol 39: 524-543.
48. Nishizawa H, Takahashi M, Fukuoka H, Iguchi G, Kitazawa R, Takahashi Y (2012) GH-independent IGF-I action is essential to prevent the development of nonalcoholic steatohepatitis in a GH-deficient rat model. Biochem Biophys Res Commun 423: 295-300.
49. Bailyes EM, Nave BT, Soos MA, Orr SR, Hayward AC, Siddle K (1997) Insulin receptor/IGF-I receptor hybrids are widely distributed in mammalian tissues: quantification of individual receptor species by selective immunoprecipitation and immunoblotting. Biochem J 327 (Pt 1): 209-215.
50. Smith BW, Adams LA (2011) Non-alcoholic fatty liver disease. Crit Rev Clin Lab Sci 48: 97-113.
51. Yakar S, Liu JL, Fernandez AM, Wu Y, Schally AV, Frystyk J, Chernausek SD, Mejia W, Le Roith D (2001) Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes 50: 1110-1118.
52. Conchillo M, de Knegt RJ, Payeras M, Quiroga J, Sangro B, Herrero JI, Castilla-Cortazar I, Frystyk J, Flyvbjerg A, Yoshizawa C, Jansen PL, Scharschmidt B, Prieto J (2005) Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: results of a pilot randomized controlled clinical trial. J Hepatol 43: 630-636.
53. Hao CN, Geng YJ, Li F, Yang T, Su DF, Duan JL, Li Y(2011) Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis. Apoptosis 16: 1118-1127.
54. Puche JE, Garcia-Fernandez M, Muntane J, Rioja J, Gonzalez-Baron S, Castilla Cortazar I (2008) Low doses of insulin-like growth factor-I induce mitochondrial protection in aging rats. Endocrinology 149: 2620-2627.
55. Perez R, Garcia-Fernandez M, Diaz-Sanchez M, Puche JE, Delgado G, Conchillo M, Muntane J, Castilla-Cortazar I (2008) Mitochondrial protection by low doses of insulin-like growth factor I in experimental cirrhosis. World J Gastroenterol 14: 2731-2739.
56. Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers JT, Depinho RA, Puigserver P, White MF (2009) Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med 15: 1307-1311.
57. Sanz S, Pucilowska JB, Liu S, Rodriguez-Ortigosa CM, Lund PK, Brenner DA, Fuller CR, Simmons JG, Pardo A, Martinez-Chantar ML, Fagin JA, Prieto J (2005) Expression of insulin-like growth factor I by activated hepatic stellate cells reduces fibrogenesis and enhances regeneration after liver injury. Gut 54: 134-141.
58. Lee UE, Friedman SL (2011) Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 25: 195-206.
59. Fujii H, Kawada N (2012) Inflammation and fibrogenesis in steatohepatitis. J Gastroenterol 47: 215-225.
60. Scharf JG, Knittel T, Dombrowski F, Muller L, Saile B, Braulke T, Hartmann H, Ramadori G (1998) Characterization of the IGF axis components in isolated rat hepatic stellate cells. Hepatology 27: 1275-1284.
61. Svegliati-Baroni G, Ridolfi F, Di Sario A, Casini A, Marucci L, Gaggiotti G, Orlandoni P, Macarri G, Perego L, Benedetti A, Folli F (1999) Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology 29: 1743-1751.
62. Brenzel A, Gressner AM (1996) Characterization ofinsulin-like growth factor (IGF)-I-receptor binding sites during in vitro transformation of rat hepatic stellate cells to myofibroblasts. Eur J Clin Chem Clin Biochem 34: 401-409.
63. Skrtic S, Wallenius V, Ekberg S, Brenzel A, Gressner AM, Jansson JO (1997) Insulin-like growth factors stimulate expression of hepatocyte growth factor but not transforming growth factor beta1 in cultured hepatic stellate cells. Endocrinology 138: 4683-4689.
64. Matsuda Y, Matsumoto K, Yamada A, Ichida T, Asakura H, Komoriya Y, Nishiyama E, Nakamura T (1997) Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis. Hepatology 26: 81-89.
65. Arturi F, Succurro E, Procopio C, Pedace E, Mannino GC, Lugara M, Procopio T, Andreozzi F, Sciacqua A, Hribal ML, Perticone F, Sesti G (2011) Nonalcoholic fatty liver disease is associated with low circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab 96: E1640-E1644.
66. Volzke H, Nauck M, Rettig R, Dorr M, Higham C, Brabant G, Wallaschofski H (2009) Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample. Eur J Endocrinol 161: 705-713.
67. Garcia-Galiano D, Sanchez-Garrido MA, Espejo I, Montero JL, Costan G, Marchal T, Membrives A, Gallardo-Valverde JM, Munoz-Castaneda JR, Arevalo E, De la Mata M, Muntane J (2007) IL-6 and IGF-1 are independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients. Obes Surg 17: 493-503.
68. Tateno C, Kataoka M, Utoh R, Tachibana A, Itamoto T, Asahara T, Miya F, Tsunoda T, Yoshizato K (2011) Growth hormone-dependent pathogenesis of human hepatic steatosis in a novel mouse model bearing a human hepatocyte-repopulated liver. Endocrinology 152: 1479-1491.
69. Le Roith D, Bondy C, Yakar S, Liu JL, Butler A (2001) The somatomedin hypothesis: 2001. Endocr Rev 22: 53-74.