Discovery and uses of pegvisomant: A growth hormone antagonist

Endokrynologia Polska

Volumn 58, Issue 4, 2007, Pages 322-329

  Berryman, Darlene E ^a   Palmer, Amanda J ^a   Gosney, Elahu S ^a   Swaminathan, Svetha ^a   DeSantis, Dave ^a   Kopchick, John J ^a  

^a OHIO UNIVERSITY   (United States)

Author keywords

Growth hormone; Growth hormone receptor; Growth hormone receptor antagonist

Indexed keywords

DRUG DERIVATIVE; GROWTH HORMONE; GROWTH HORMONE RECEPTOR; HORMONE ANTAGONIST; HUMAN GROWTH HORMONE; PEGVISOMANT;

ANIMAL; CHEMICAL STRUCTURE; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; PHYSIOLOGY; REVIEW;

ANIMALS; GROWTH HORMONE; HORMONE ANTAGONISTS; HUMAN GROWTH HORMONE; HUMANS; MODELS, MOLECULAR; RECEPTORS, SOMATOTROPIN;

EID: 38449118318     PISSN: 0423104X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (91)

1. Hill DJ, Riley SC, Bassett NS et al. Localization of the growth hormone receptor, identified by immunocytochemistry, in second trimester human fetal tissues and in placenta throughout gestation. J Clin Endocrinol Metab 1992; 75 (2): 646-650.
2. Mercado M, DaVila N, McLeod JF et al. Distribution of growth hormone receptor messenger ribonucleic acid containing and lacking exon 3 in human tissues. J Clin Endocrinol Metab 1994; 78 (3): 731-735.
3. Mertani HC, Morel G. In situ gene expression of growth hormone (GH) receptor and GH binding protein in adult male rat tissues. Mol Cell Endocrinol 1995; 109 (1): 47-61.
4. Nyberg F, Burman P. Growth hormone and its receptors in the central nervous system-location and functional significance. Horm Res 1996; 45 (1-2): 18-22.
5. Rapaport R, Sills IN, Green L et al. Detection of human growth hormone receptors on IM-9 cells and peripheral blood mononuclear cell subsets by flow cytometry: correlation with growth hormone-binding protein levels. J Clin Endocrinol Metab 1995; 80 (9): 2612-2619.
6. Kopchick JJ, Andry JM. Growth hormone (GH), GH receptor, and signal transduction. Mol Genet Metab 2000; 71 (1-2): 293-314.
7. Goodman HM. Multiple effects of growth hormone on lipolysis. Endocrinology 1968; 83 (2): 300-308.
8. Green H, Morikawa M, Nixon T. A dual effector theory of growth-hormone action. Differentiation 1985; 29 (3): 195-198.
9. Gharib H, Cook DM, Saenger PH et al. American Association of Clinical Endocrinologists medical guidelines for clinical prac tice for growth hormone use in adults and children-2003 update. Endocr Pract 2003; 9 (1): 64-76.
10. Molitch ME, Clemmons DR, Malozowski S et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2006; 91 (5): 1621-1634.
11. Clayton PE, Cianfarani S, Czernichow P et al. Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 2007; 92 (3): 804-810.
12. INCRELEX™ Package Insert. 2005.
13. Abdel-Meguid SS, Shieh HS, Smith WW et al. Three-dimensional structure of a genetically engineered variant of porcine growth hormone. Proc Natl Acad Sci USA 1987; 84 (18): 6434-6437.
14. de Vos AM, Ultsch M, Kossiakoff AA. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 1992; 255 (5042): 306-312.
15. Chen XZ, Shafer AW, Yun JS et al. Conversion of bovine growth hormone cysteine residues to serine affects secretion by cultured cells and growth rates in transgenic mice. Mol Endocrinol 1992; 6 (4): 598-606.
16. Hara K, Hsu Chen CJ, Sonenberg M. Recombination of the biologically active peptides from a tryptic digest of bovine growth hormone. Biochemistry 1978; 17 (3): 550-556.
17. Bazan JF. Haemopoietic receptors and helical cytokines. Immunol Today 1990; 11 (10): 350-354.
18. Leung DW, Spencer SA, Cachianes G et al. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature 1987; 330 (6148): 537-543.
19. Cunningham BC, Ultsch M, De Vos AM et al. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 1991; 254 (5033): 821-825.
20. Harding PA, Wang X, Okada S et al. Growth hormone (GH) and a GH antagonist promote GH receptor dimerization and internalization. J Biol Chem 1996; 271 (12): 6708-6712.
21. Ross RJ, Leung KC, Maamra M et al. Binding and functional studies with the growth hormone receptor antagonist, B2036-PEG (pegvisomant), reveal effects of pegylation and evidence that it binds to a receptor dimer. J Clin Endocrinol Metab 2001; 86 (4): 1716-1723.
22. Gent J, van Kerkhof P, Roza M et al. Ligand-independent growth hormone receptor dimerization occurs in the endoplasmic reticulum and is required for ubiquitin system-dependent endocytosis. Proc Natl Acad Sci USA 2002; 99 (15): 9858-9863.
23. Brown RJ, Adams JJ, Pelekanos RA et al. Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol 2005; 12 (9): 814-821.
24. Cunningham BC, Jhurani P, Ng P et al. Receptor and antibody epitopes in human growth hormone identified by homologscanning mutagenesis. Science 1989; 243 (4896): 1330-1336.
25. Cunningham BC, Wells JA. High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis. Science 1989; 244 (4908): 1081-1085.
26. Pearce KH Jr, Ultsch MH, Kelley RF et al. Structural and mutational analysis of affinity-inert contact residues at the growth hormone-receptor interface. Biochemistry 1996; 35 (32): 10 300-10 307.
27. Fuh G, Cunningham BC, Fukunaga R et al. Rational design of potent antagonists to the human growth hormone receptor. Science 1992; 256 (5064): 1677-1680.
28. Bass SH, Mulkerrin MG, Wells JA. A systematic mutational analysis of hormone-binding determinants in the human growth hormone receptor. Proc Natl Acad Sci USA 1991; 88 (10): 4498-4502.
29. Chen WY, Wight DC, Chen NY et al. 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 (4): 2252-2258.
30. Chen WY, Wight DC, Wagner TE et al. Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci USA 1990; 87 (13): 5061-5065.
31. Chen WY, Wight DC, Mehta BV et al. Glycine 119 of bovine growth hormone is critical for growth-promoting activity. Mol Endocrinol 1991; 5 (12): 1845-1852.
32. Chen WY, White ME, Wagner TE et al. Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice. Endocrinology 1991; 129 (3): 1402-1408.
33. Harding PA, Wang X, Okada S et al. Growth hormone (GH) and a GH antagonist promote GH receptor dimerization and internalization. J Biol Chem 1996; 271 (12): 6708-6712.
34. Clark R, Olson K, Fuh G et al. Long-acting growth hormones produced by conjugation with polyethylene glycol. J Biol Chem 1996; 271 (36): 21969-21977.
35. Lowman HB, Wells JA. Affinity maturation of human growth hormone by monovalent phage display. J Mol Biol 1993; 234 (3): 564-578.
36. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342 (16): 1171-1177.
37. van der Lely AJ, Hutson RK, Trainer PJ et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001; 358 (9295): 1754-1759.
38. Kopchick JJ, Parkinson C, Stevens EC et al. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr Rev 2002; 23 (5): 623-646.
39. Kopchick JJ. Discovery and mechanism of action of pegvisomant. Eur J Endocrinol 2003; 148 (supl 2): S21-S25.
40. Muller AF, van der Lely AJ. Pharmacological therapy for acromegaly: a critical review. Drugs 2004; 64 (16): 1817-1838.
41. Paisley AN, Trainer PJ, Drake WM. The place of pegvisomant in the acromegaly treatment algorithm. Growth Horm IGF Res 2004; 14 (supl A): S101-S106.
42. van der Lely AJ, Kopchick JJ. Growth hormone receptor antagonists. Neuroendocrinology 2006; 83 (3-4): 264-268.
43. Paisley AN, Drake WM. Treatment of pituitary tumors: pegvisomant. Endocrine 2005; 28 (1): 111-114.
44. Paisley AN, Trainer PJ. Recent developments in the therapy of acromegaly. Expert Opin Investig Drugs 2006; 15 (3): 251-256.
45. Burt MG, Ho KK. Newer options in the management of acromegaly. Intern Med J 2006; 36 (7): 437-444.
46. Houssay B, Biasotti A. The hypothesis, carbohydrate metabolism and diabetes. Endocrinology 1931; 15: 511.
47. Hansen I, Tsalikian E, Beaufrere B et al. Insulin resistance in acromegaly: defects in both hepatic and extrahepatic insulin action. Am J Physiol 1986; 250 (3 Pt 1): E269-E273.
48. Davidson MB. Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 1987; 8 (2): 115-131.
49. Foss MC, Saad MJ, Paccola GM et al. Peripheral glucose metabolism in acromegaly. J Clin Endocrinol Metab 1991; 72 (5): 1048-1053.
50. Strawbridge RJ, Karvestedt L, Li C et al. GHR exon 3 polymorphism: association with type 2 diabetes mellitus and metabolic disorder. Growth Horm IGF Res 2007.
51. Coschigano KT, Clemmons D, Bellush LL et al. Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 2000; 141 (7): 2608-2613.
52. Berryman DE, List EO, Coschigano KT et al. Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res 2004; 14 (4): 309-318.
53. Olsson B, Bohlooly YM, Fitzgerald SM et al. Bovine growth hormone transgenic mice are resistant to diet-induced obesity but develop hyperphagia, dyslipidemia, and diabetes on a highfat diet. Endocrinology 2005; 146 (2): 920-930.
54. Mauvais-Jarvis F, Ueki K, Fruman DA et al. Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest 2002; 109 (1): 141-149.
55. Cornier MA, Bessesen DH, Gurevich I et al. Nutritional upregulation of p85alpha expression is an early molecular manifestation of insulin resistance. Diabetologia 2006; 49 (4): 748-754.
56. Barbour LA, Mizanoor Rahman S, Gurevich I et al. Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess. J Biol Chem 2005; 280 (45): 37 489-37 494.
57. Taniguchi CM, Tran TT, Kondo T et al. Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. Proc Natl Acad Sci USA 2006; 103 (32): 12 093-12 097.
58. del Rincon JP, Iida K, Gaylinn BD et al. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormonemediated insulin resistance. Diabetes 2007; 56 (6): 1638-1646.
59. Parkinson C, Drake WM, Roberts ME et al. A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal. J Clin Endocrinol Metab 2002; 87 (4): 1797-1804.
60. Rose DR, Clemmons DR. Growth hormone receptor antagonist improves insulin resistance in acromegaly. Growth Horm IGF Res 2002; 12 (6): 418-424.
61. Drake WM, Rowles SV, Roberts ME et al. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol 2003; 149 (6): 521-547.
62. Colao A, Pivonello R, Auriemma RS et al. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol 2006; 154 (3): 467-477.
63. Lindberg-Larsen R, Moller N, Schmitz O et al. The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly. J Clin Endocrinol Metab 2007; 92 (5): 1724-1728.
64. Williams RM, Amin R, Shojaee-Moradie F et al. The effects of a specific growth hormone antagonist on overnight insulin requirements and insulin sensitivity in young adults with Type 1 diabetes mellitus. Diabetologia 2003; 46 (9): 1203-1210.
65. 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 (11): 5163-5165.
66. Flyvbjerg A, Bennett WF, Rasch R et al. 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.
67. Segev Y, Landau D, Rasch R et al. Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice. J Am Soc Nephrol 1999; 10 (11): 2374-2381.
68. Flyvbjerg A, Bennett WF, Rasch R et al. Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent. Kidney Int 1999; 56 (6): 2048-2054.
69. van Neck JW, Dits NF, Cingel V et al. Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/ insulin-like growth factor system in adult mice. J Endocrinol 2000; 167 (2): 295-303.
70. Sraer JD, Delarue F, Hagege J et al. Stable cell lines of T-SV40 immortalized human glomerular mesangial cells. Kidney Int 1996; 49 (1): 267-270.
71. Mene P, Simonson MS, Dunn MJ. Physiology of the mesangial cell. Physiol Rev 1989; 69 (4): 1347-1424.
72. Meinhardt U, Eble A, Besson A et al. Regulation of growth-hormone- receptor gene expression by growth hormone and pegvisomant in human mesangial cells. Kidney Int 2003; 64 (2): 421-430.
73. Poulsen J. The Houssay phenomenon in man: recovery from retinopathy in a case of diabetes with Simmond's disease. Diabetes 1953; 2: 7-12.
74. Poulsen JE. Diabetes and anterior pituitary insufficiency. Final course and postmortem study of a diabetic patient with Sheehan's syndrome. Diabetes 1966; 15 (2): 73-77.
75. Merimee TJ. A follow-up study of vascular disease in growthhormone- deficient dwarfs with diabetes. N Engl J Med 1978; 298 (22): 1217-1222.
76. Smith LE, Kopchick JJ, Chen W et al. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 1997; 276 (5319): 1706-1709.
77. The Growth Hormone Antagonist for Proliferate Diabetic Retinopathy Study Group. The effect of a growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology 2001; 108 (12): 2266-2272.
78. Sesmilo G, Fairfield WP, Katznelson L et al. Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. J Clin Endocrinol Metab 2002; 87 (4): 1692-1699.
79. Pivonello R, Galderisi M, Auriemma RS et al. Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance. J Clin Endocrinol Metab 2007; 92 (2): 476-482.
80. Pollak M. Insulin-like growth factor physiology and cancer risk. Eur J Cancer 2000; 36 (10): 1224-1228.
81. Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004; 4 (7): 505-518.
82. Khandwala HM, McCutcheon IE, Flyvbjerg A et al. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 2000; 21 (3): 215-244.
83. Kaulsay KK, Mertani HC, Tornell J et al. Autocrine stimulation of human mammary carcinoma cell proliferation by human growth hormone. Exp Cell Res 1999; 250 (1): 35-50.
84. Pollak M, Blouin MJ, Zhang JC et al. Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist. Br J Cancer 2001; 85 (3): 428-430.
85. Zhang X, Mehta RG, Lantvit DD et al. Inhibition of estrogenindependent mammary carcinogenesis by disruption of growth hormone signaling. Carcinogenesis 2007; 28 (1): 143-150.
86. Shen Q, Lantvit DD, Lin Q et al. Advanced rat mammary cancers are growth hormone dependent. Endocrinology 2007; epub ahead of press.
87. Divisova J, Kuiatse I, Lazard Z et al. The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth. Breast Cancer Res Treat 2006; 98 (3): 315-327.
88. McCutcheon IE, Flyvbjerg A, Hill H et al. Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice. J Neurosurg 2001; 94 (3): 487-492.
89. Dagnaes-Hansen F, Duan H, Rasmussen LM et al. Growth hormone receptor antagonist administration inhibits growth of human colorectal carcinoma in nude mice. Anticancer Research 2004; 24 (6): 3735-3742.
90. Wang Z, Prins GS, Coschigano KT et al. Disruption of growth hormone signaling retards early stages of prostate carcinogenesis in the C3(1)/T antigen mouse. Endocrinology 2005; 146 (12): 5188-5196.
91. Berryman DE, Kopchick JJ. Discovery of a growth hormone antagonist using a structure-function approach. In: Golemis EA, Adams PD (ed). Protein-Protein Interactions: A Molecular Cloning Manual. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. 2005; 873-884.