1. Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, Okada S, Cataldo L, Coschigamo K, Wagner TE, Baumann G, Kopchick JJ. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci U S A. 1997. 94:13215–13220.
2. List EO, Sackmann-Sala L, Berryman DE, Funk K, Kelder B, Gosney ES, Okada S, Ding J, Cruz-Topete D, Kopchick JJ. Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR-/-) mouse. Endocr Rev. 2011. 32:356–386.
3. Berryman DE, List EO, Kohn DT, Coschigano KT, Seeley RJ, Kopchick JJ. Effect of growth hormone on susceptibility to diet-induced obesity. Endocrinology. 2006. 147:2801–2808.
4. Panici JA, Wang F, Bonkowski MS, Spong A, Bartke A, Pawlikowska L, Kwok PY, Masternak MM. Is altered expression of hepatic insulin-related genes in growth hormone receptor knockout mice due to GH resistance or a difference in biological life spans? J Gerontol A Biol Sci Med Sci. 2009. 64:1126–1133.
5. Egecioglu E, Bjursell M, Ljungberg A, Dickson SL, Kopchick JJ, Bergström G, Svensson L, Oscarsson J, Törnell J, Bohlooly-Y M. Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice. Am J Physiol Endocrinol Metab. 2006. 290:E317–E325.
6. Liu JL, Coschigano KT, Robertson K, Lipsett M, Guo Y, Kopchick JJ, Kumar U, Liu YL. Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice. Am J Physiol Endocrinol Metab. 2004. 287:E405–E413.
7. Bartke A, Peluso MR, Moretz N, Wright C, Bonkowski M, Winters TA, Shanahan MF, Kopchick JJ, Banz WJ. Effects of soy-derived diets on plasma and liver lipids, glucose tolerance, and longevity in normal, long-lived and short-lived mice. Horm Metab Res. 2004. 36:550–558.
8. Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology. 2003. 144:3799–3810.
9. Hauck SJ, Hunter WS, Danilovich N, Kopchick JJ, Bartke A. Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse. Exp Biol Med (Maywood). 2001. 226:552–558.
10. Dominici FP, Arostegui Diaz G, Bartke A, Kopchick JJ, Turyn D. Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice. J Endocrinol. 2000. 166:579–590.
11. Bonkowski MS, Dominici FP, Arum O, Rocha JS, Al Regaiey KA, Westbrook R, Spong A, Panici J, Masternak MM, Kopchick JJ, Bartke A. Disruption of growth hormone receptor prevents calorie restriction from improving insulin action and longevity. PLoS One. 2009. 4:e4567.
12. Al-Regaiey KA, Masternak MM, Bonkowski M, Sun L, Bartke A. Longlived growth hormone receptor knockout mice: interaction of reduced insulin-like growth factor i/insulin signaling and caloric restriction. Endocrinology. 2005. 146:851–860.
13. Berryman DE, List EO, Coschigano KT, Behar K, Kim JK, Kopchick JJ. Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res. 2004. 14:309–318.
14. Berryman DE, List EO, Palmer AJ, Chung MY, Wright-Piekarski J, Lubbers E, O'Connor P, Okada S, Kopchick JJ. Two-year body composition analyses of long-lived GHR null mice. J Gerontol A Biol Sci Med Sci. 2010. 65:31–40.
15. Nilsson L, Binart N, Bohlooly-Y M, Bramnert M, Egecioglu E, Kindblom J, Kelly PA, Kopchick JJ, Ormandy CJ, Ling C, Billig H. Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Biochem Biophys Res Commun. 2005. 331:1120–1126.
16. Tran TT, Yamamoto Y, Gesta S, Kahn CR. Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 2008. 7:410–420.
17. Huffman DM, Barzilai N. Contribution of adipose tissue to health span and longevity. Interdiscip Top Gerontol. 2010. 37:1–19.
18. Bellush LL, Doublier S, Holland AN, Striker LJ, Striker GE, Kopchick JJ. Protection against diabetes-induced nephropathy in growth hormone receptor/binding protein gene-disrupted mice. Endocrinology. 2000. 141:163–168.
19. Ikeno Y, Hubbard GB, Lee S, Cortez LA, Lew CM, Webb CR, Berryman DE, List EO, Kopchick JJ, Bartke A. Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J Gerontol A Biol Sci Med Sci. 2009. 64:522–529.
20. Laron Z, Blum W, Chatelain P, Ranke M, Rosenfeld R, Savage M, Underwood L. Classification of growth hormone insensitivity syndrome. J Pediatr. 1993. 122:241.
21. Arman A, Yüksel B, Coker A, Sarioz O, Temiz F, Topaloglu AK. Novel growth hormone receptor gene mutation in a patient with Laron syndrome. J Pediatr Endocrinol Metab. 2010. 23:407–414.
22. Laron Z, Kopchick JJ. Laron syndrome: from man to mouse. 2011. Berlin: Springer.
23. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, Hwang D, Martin-Montalvo A, Saavedra J, Ingles S, de Cabo R, Cohen P, Longo VD. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011. 3:70ra13.
24. Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM. Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature. 1982. 300:611–615.
25. Kaps M, Moura AS, Safranski TJ, Lamberson WR. Components of growth in mice hemizygous for a MT/bGH transgene. J Anim Sci. 1999. 77:1148–1154.
26. Knapp JR, Chen WY, Turner ND, Byers FM, Kopchick JJ. Growth patterns and body composition of transgenic mice expressing mutated bovine somatotropin genes. J Anim Sci. 1994. 72:2812–2819.
27. Palmer AJ, Chung MY, List EO, Walker J, Okada S, Kopchick JJ, Berryman DE. Age-related changes in body composition of bovine growth hormone transgenic mice. Endocrinology. 2009. 150:1353–1360.
28. Kopchick JJ, Bellush LL, Coschigano KT. Transgenic models of growth hormone action. Annu Rev Nutr. 1999. 19:437–461.
29. Wang Z, Masternak MM, Al-Regaiey KA, Bartke A. Adipocytokines and the regulation of lipid metabolism in growth hormone transgenic and calorie-restricted mice. Endocrinology. 2007. 148:2845–2853.
30. Olsson B, Bohlooly-Y M, Fitzgerald SM, Frick F, Ljungberg A, Ahrén B, Törnell J, Bergström G, Oscarsson J. Bovine growth hormone transgenic mice are resistant to diet-induced obesity but develop hyperphagia, dyslipidemia, and diabetes on a high-fat diet. Endocrinology. 2005. 146:920–930.
31. Pomp D, Oberbauer AM, Murray JD. Development of obesity following inactivation of a growth hormone transgene in mice. Transgenic Res. 1996. 5:13–23.
32. Eckstein F, Lochmüller EM, Koller B, Wehr U, Weusten A, Rambeck W, Hoeflich A, Wolf E. Body composition, bone mass and microstructural analysis in GH-transgenic mice reveals that skeletal changes are specific to bone compartment and gender. Growth Horm IGF Res. 2002. 12:116–125.
33. Bartke A. Can growth hormone (GH) accelerate aging? Evidence from GHtransgenic mice. Neuroendocrinology. 2003. 78:210–216.
34. Wolf E, Kahnt E, Ehrlein J, Hermanns W, Brem G, Wanke R. Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: lessons from transgenic animal models. Mech Ageing Dev. 1993. 68:71–87.
35. Orian JM, Lee CS, Weiss LM, Brandon MR. The expression of a metallothionein-ovine growth hormone fusion gene in transgenic mice does not impair fertility but results in pathological lesions in the liver. Endocrinology. 1989. 124:455–463.
36. Quaife CJ, Mathews LS, Pinkert CA, Hammer RE, Brinster RL, Palmiter RD. Histopathology associated with elevated levels of growth hormone and insulin-like growth factor I in transgenic mice. Endocrinology. 1989. 124:40–48.
37. Shea BT, Hammer RE, Brinster RL. Growth allometry of the organs in giant transgenic mice. Endocrinology. 1987. 121:1924–1930.
38. Machado MO, Hirata RD, Sellitti DF, Iotti R, Iotti A, Cusumano AM, Riordan GP, Coschigano KT, Kopchick JJ, Zuhl I, Nguyen N, Hirata MH, Doi SQ. Growth hormone promotes glomerular lipid accumulation in bGH mice. Kidney Int. 2005. 68:2019–2028.
39. Yang CW, Striker LJ, Pesce C, Chen WY, Peten EP, Elliot S, Doi T, Kopchick JJ, Striker GE. Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone. Studies in transgenic mice. Lab Invest. 1993. 68:62–70.
40. Yang CW, Striker LJ, Kopchick JJ, Chen WY, Pesce CM, Peten EP, Striker GE. Glomerulosclerosis in mice transgenic for native or mutated bovine growth hormone gene. Kidney Int Suppl. 1993. 39:S90–S94.
41. Liu ZH, Striker LJ, Phillips C, Chen NY, Chen WY, Kopchick JJ, Striker GE. Growth hormone expression is required for the development of diabetic glomerulosclerosis in mice. Kidney Int Suppl. 1995. 51:S37–S38.
42. Izzard AS, Emerson M, Prehar S, Neyses L, Trainer P, List EO, Kopchick JJ, Heagerty AM. The cardiovascular phenotype of a mouse model of acromegaly. Growth Horm IGF Res. 2009. 19:413–419.
43. Miquet JG, Giani JF, Martinez CS, Muñoz MC, González L, Sotelo AI, Boparai RK, Masternak MM, Bartke A, Dominici FP, Turyn D. Prolonged exposure to GH impairs insulin signaling in the heart. J Mol Endocrinol. 2011. 47:167–177.
44. Bohlooly-Y M, Olsson B, Bruder CE, Lindén D, Sjögren K, Bjursell M, Egecioglu E, Svensson L, Brodin P, Waterton JC, Isaksson OG, Sundler F, Ahrén B, Ohlsson C, Oscarsson J, Törnell J. Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia. Diabetes. 2005. 54:51–62.
45. Bollano E, Omerovic E, Bohlooly-y M, Kujacic V, Madhu B, Törnell J, Isaksson O, Soussi B, Schulze W, Fu ML, Matejka G, Waagstein F, Isgaard J. Impairment of cardiac function and bioenergetics in adult transgenic mice overexpressing the bovine growth hormone gene. Endocrinology. 2000. 141:2229–2235.
46. Frick F, Bohlooly-Y M, Lindén D, Olsson B, Törnell J, Edén S, Oscarsson J. Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice. Am J Physiol Endocrinol Metab. 2001. 281:E1230–E1239.
47. Doi T, Striker LJ, Kimata K, Peten EP, Yamada Y, Striker GE. Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels. J Exp Med. 1991. 173:1287–1290.
48. Kumar PA, Brosius FC 3rd, Menon RK. The glomerular podocyte as a target of growth hormone action: implications for the pathogenesis of diabetic nephropathy. Curr Diabetes Rev. 2011. 7:50–55.
49. Cecim M, Bartke A, Yun JS, Wagner TH. Expression of human, but not bovine, growth hormone genes promotes development of mammary tumors in transgenic mice. Transgenics. 1994. 1:431–437.
50. Sherlock M, Woods C, Sheppard MC. Medical therapy in acromegaly. Nat Rev Endocrinol. 2011. 7:291–300.
51. Chen WY, White ME, Wagner TE, Kopchick JJ. Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice. Endocrinology. 1991. 129:1402–1408.
52. Chen WY, Wight DC, Chen NY, Coleman TA, Wagner TE, Kopchick JJ. Mutations in the third alpha-helix of bovine growth hormone dramatically affect its intracellular distribution in vitro and growth enhancement in transgenic mice. J Biol Chem. 1991. 266:2252–2258.
53. Chen WY, Wight DC, Mehta BV, Wagner TE, Kopchick JJ. Glycine 119 of bovine growth hormone is critical for growth-promoting activity. Mol Endocrinol. 1991. 5:1845–1852.
54. Okada S, Chen WY, Wiehl P, Kelder B, Goodman HM, Guller S, Sonenberg M, Kopchick JJ. A growth hormone (GH) analog can antagonize the ability of native GH to promote differentiation of 3T3-F442A preadipocytes and stimulate insulin-like and lipolytic activities in primary rat adipocytes. Endocrinology. 1992. 130:2284–2290.
55. de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992. 255:306–312.
56. Cunningham BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science. 1991. 254:821–825.
57. Cunningham BC, Jhurani P, Ng P, Wells JA. Receptor and antibody epitopes in human growth hormone identified by homolog-scanning mutagenesis. Science. 1989. 243:1330–1336.
58. Cunningham BC, Wells JA. High-resolution epitope mapping of hGHreceptor interactions by alanine-scanning mutagenesis. Science. 1989. 244:1081–1085.
59. Pearce KH Jr, Ultsch MH, Kelley RF, de Vos AM, Wells JA. Structural and mutational analysis of affinity-inert contact residues at the growth hormone-receptor interface. Biochemistry. 1996. 35:10300–10307.
60. Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA. Rational design of potent antagonists to the human growth hormone receptor. Science. 1992. 256:1677–1680.
61. Bass SH, Mulkerrin MG, Wells JA. A systematic mutational analysis of hormone-binding determinants in the human growth hormone receptor. Proc Natl Acad Sci U S A. 1991. 88:4498–4502.
62. Hara K, Hsu Chen CJ, Sonenberg M. Recombination of the biologically active peptides from a tryptic digest of bovine growth hormone. Biochemistry. 1978. 17:550–556.
63. Chen WY, Wight DC, Wagner TE, Kopchick JJ. Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci U S A. 1990. 87:5061–5065.
64. Yakar S, Setser J, Zhao H, Stannard B, Haluzik M, Glatt V, Bouxsein ML, Kopchick JJ, LeRoith D. Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. J Clin Invest. 2004. 113:96–105.
65. Veldhuis JD, Bidlingmaier M, Anderson SM, Evans WS, Wu Z, Strasburger CJ. Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men. J Clin Endocrinol Metab. 2002. 87:5737–5745.
66. Clark R, Olson K, Fuh G, Marian M, Mortensen D, Teshima G, Chang S, Chu H, Mukku V, Canova-Davis E, Somers T, Cronin M, Winkler M, Wells JA. Long-acting growth hormones produced by conjugation with polyethylene glycol. J Biol Chem. 1996. 271:21969–21977.
67. Pradhananga S, Wilkinson I, Ross RJ. Pegvisomant: structure and function. J Mol Endocrinol. 2002. 29:11–14.
68. Muller AF, Kopchick JJ, Flyvbjerg A, van der Lely AJ. Clinical review 166: growth hormone receptor antagonists. J Clin Endocrinol Metab. 2004. 89:1503–1511.
69. Goffin V, Bernichtein S, Carrière O, Bennett WF, Kopchick JJ, Kelly PA. The human growth hormone antagonist B2036 does not interact with the prolactin receptor. Endocrinology. 1999. 140:3853–3856.
70. Mode A, Tollet P, Wells T, Carmignac DF, Clark RG, Chen WY, Kopchick JJ, Robinson IC. The human growth hormone (hGH) antagonist G120Rh-GH does not antagonize GH in the rat, but has paradoxical agonist activity, probably via the prolactin receptor. Endocrinology. 1996. 137:447–454.
71. Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr Rev. 2002. 23:623–646.
72. Wilson ME. Effects of estradiol and exogenous insulin-like growth factor I (IGF-I) on the IGF-I axis during growth hormone inhibition and antagonism. J Clin Endocrinol Metab. 1998. 83:4013–4021.
73. Wilson ME. Insulin-like growth factor I (IGF-I) replacement during growth hormone receptor antagonism normalizes serum IGF-binding protein-3 and markers of bone formation in ovariectomized rhesus monkeys. J Clin Endocrinol Metab. 2000. 85:1557–1562.
74. Thorner MO, Strasburger CJ, Wu Z, Straume M, Bidlingmaier M, Pezzoli SS, Zib K, Scarlett JC, Bennett WF. Growth hormone (GH) receptor blockade with a PEG-modified GH (B2036-PEG) lowers serum insulin-like growth factor-I but does not acutely stimulate serum GH. J Clin Endocrinol Metab. 1999. 84:2098–2103.
75. van der Lely AJ, Lamberts SW, Barkan A, Panadya N, Besser GM, Trainer P, Bonnert V, Melmed S, Clemmons D, Rose R, Vance ML, Thorner MO, Zib K, Davis RJ, Bennett W, Scarlett JA. A six week, double blind, placebo controlled study of a growth hormone antagonist, B2036-PEG (Trovert) in acromegalic patients. Proceedings of the 80th Annual Meeting of the Endocrine Society. 1998 June 24-27; New Orleans, LA. –57.
76. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000. 342:1171–1177.
77. van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001. 358:1754–1759.
78. Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005. 90:5684–5691.
79. Trainer PJ. ACROSTUDY: the first 5 years. Eur J Endocrinol. 2009. 161:Suppl 1. S19–S24.
80. Bartke A, Brown-Borg HM, Bode AM, Carlson J, Hunter WS, Bronson RT. Does growth hormone prevent or accelerate aging. Exp Gerontol. 1998. 33:675–687.
81. Palmiter RD, Norstedt G, Gelinas RE, Hammer RE, Brinster RL. Metallothionein-human GH fusion genes stimulate growth of mice. Science. 1983. 222:809–814.
82. Olsson B, Bohlooly-Y M, Brusehed O, Isaksson OG, Ahrén B, Olofsson SO, Oscarsson J, Törnell J. Bovine growth hormone-transgenic mice have major alterations in hepatic expression of metabolic genes. Am J Physiol Endocrinol Metab. 2003. 285:E504–E511.
83. Cecim M, Fadden C, Kerr J, Steger RW, Bartke A. Infertility in transgenic mice overexpressing the bovine growth hormone gene: disruption of the neuroendocrine control of prolactin secretion during pregnancy. Biol Reprod. 1995. 52:1187–1192.
84. Chen NY, Chen WY, Kopchick JJ. A growth hormone antagonist protects mice against streptozotocin induced glomerulosclerosis even in the presence of elevated levels of glucose and glycated hemoglobin. Endocrinology. 1996. 137:5163–5165.
85. Flyvbjerg A, Bennett WF, Rasch R, Kopchick JJ, Scarlett JA. Inhibitory effect of a growth hormone receptor antagonist (G120K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice. Diabetes. 1999. 48:377–382.
86. Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology. 2003. 144:3799–3810.
87. Berryman DE, List EO, Sackmann-Sala L, Lubbers E, Munn R, Kopchick JJ. Growth hormone and adipose tissue: beyond the adipocyte. Growth Horm IGF Res. 2011. 21:113–123.