GH receptor antagonist: Mechanism of action and clinical utility

Reviews in Endocrine and Metabolic Disorders

Volumn 6, Issue 1, 2005, Pages 5-13

  Surya, Sowmya K ^a   Barkan, Ariel L ^a  

^a UNIVERSITY OF MICHIGAN HOSPITALS   (United States)

Author keywords

Acromegaly; GH receptor antagonists; Pegvisomant

Indexed keywords

ANGIOPEPTIN; BROMOCRIPTINE; CABERGOLINE; DOPAMINE RECEPTOR STIMULATING AGENT; ESTROGEN; GROWTH HORMONE RECEPTOR ANTAGONIST; GUINAGOLIDE; HORMONE RECEPTOR BLOCKING AGENT; MACROGOL 5000; OCTAPEPTIDE; OCTREOTIDE; ORAL ANTIDIABETIC AGENT; PASIREOTIDE; PEGVISOMANT; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SOMATOMEDIN; SOMATOSTATIN; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ACROMEGALY; BLEEDING; CANCER; CEREBROSPINAL FLUID RHINORRHEA; CLINICAL TRIAL; DIABETES MELLITUS; DIABETIC RETINOPATHY; DIARRHEA; DISEASE EXACERBATION; DRUG COST; DRUG EFFECT; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; GALLSTONE; GROWTH HORMONE RELEASE; HORMONE SUBSTITUTION; HUMAN; HYPOPITUITARISM; LIVER DYSFUNCTION; LIVER FUNCTION TEST; META ANALYSIS; NAUSEA; NONHUMAN; PAIN; POSTOPERATIVE COMPLICATION; REVIEW; SIDE EFFECT; SINUSITIS; TACHYPHYLAXIS; TUMOR VOLUME; VISUAL IMPAIRMENT;

ACROMEGALY; ANIMALS; DIABETIC NEPHROPATHIES; HORMONE ANTAGONISTS; HUMAN GROWTH HORMONE; HUMANS; INSULIN-LIKE GROWTH FACTOR I; NEOPLASMS; RECEPTORS, SOMATOTROPIN; SOMATOSTATIN;

EID: 17644382943     PISSN: 13899155     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11154-005-5219-x     Document Type: Review

References (67)

1. Melmed S. Acromegaly. The New England Journal of Medicine April 5, 1990:966-977.
2. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: Epidemiology, pathogenesis and management. Endocirine Reviews 2004;25:102-115.
3. Biermasz NR, Dekker FW, Pereira AM, Van Thiel SW, Schutte PJ, Van Dulken H, Romijn JA, Roelfsema FJ. Determinants of survival in treated acromegaly in a single center: Predictive value of serial insulin-like growth factorl measurements. Clin Endocrinol Metab 2004;89:2789-2796.
4. Holdaway IM, Stewart AW. Long term treatment outcome in acromegaly. Growth Hormone and IGF Research 2003;13:185-192.
5. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 2004; 89:667-674.
6. Dobrashian RD, O'Halloran DJ, Hunt A, Beardwell CG, Shalet SM. Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin Endocrinol (Oxf) 1993;38:589-593.
7. Barkan AL. Biochemical markers of acromegaly: GH vs. IGF-I. Growth Harm IGF Res 2004;14(Suppl A):S97-S100.
8. Freda PU, Nuruzzaman AT, Reyes CM, Sundeen RE, Post KD. Significance of "abnormal" nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab 2004;89:495-500.
9. Dimaraki EV, Chandler WF, Barkan AL. Acromegaly with apparently normal GH. Implications for diagnosis and follow up. J Clin Endocrinol Metab 2001;87;3537-3544.
10. Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 1998;89:353-338.
11. Freda PU, Post KD, Powell JS, Wardlaw SL. Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 1998;83:3808-3816.
12. Melmed S, Casanueva FF, Cavagnini F, Chanson P, Frohman L, Grossman A, Ho K, Kleinberg D, Lamberts S, Laws E, Lombardi G, Vance ML, Werder KV, Wass J, Giustina A. Guidelines for acromegaly management. Acromegaly Treatment Consensus Workshop Participants. J Clin Endocrinol Metab 2002;87:4054-4058.
13. Abosch A, Tyrrell JB, Lamborn KR, Hannegan LT, Applebury CB, Wilson CB, Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: Initial outcome and long-term results. J Clin Endocrinol Metab 1998;83:3411-3418.
14. Swearingen B, Barker FG 2nd, Katznelson L, Biller BM, Grinspoon S, Klibanski A, Moayeri N, Black PM, Zervas NT. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998;83:3419-3426.
15. Biermasz NR, van Dulken H, Roelfsema. Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly. J Clin Endocrinol Metab 2000;85:2476-2478.
16. Biermasz NR, Dulken HV, Roelfsema F. Postoperative radiotherapy in acromegaly is effective in reducing GH concentration to safe levels. Clin Endocrinol (Oxf) 2000;53:321-327.
17. Vladyka V, Liscak R, Simonova G, Urgosik D, Chytka T, Vymazal J, Novotny J, Marek J, Hana V. Gamma Knife (GK) radiosurgery for pituitary adenomas: Evaluation of a series of 163 patients. J Radiosurg 2000;3:113-131.
18. Barkan AL, Halasz I, Dornfeld KJ, Jaffe CA, Friberg RD, Chandler WF, Sandler HM Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 1997;82:3187-3191.
19. Barkan AL. Radiotherapy in acromegaly: The argument against. Clin Endocrinol 2003;58:132-135.
20. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab 2004;89(4):1613-1617.
21. Brada M, Ford D, Ashley S, Bliss JM, Crowley S, Mason M, Rajan B, Traish D. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Br Med J 1992;304:1343-1346.
22. Swords FM, Monson JP. Stereotactic radiosurgery: A treatment for previously radiated pituitary adenomas. J Clin Endocrinol Metab 2003;88:5334-5340.
23. Attansio R, Arosio M. Gamma knife radiosurgery in acromegaly: A 4 year follow up study. J Clin Endocrinol Metab 88:3105-3112.
24. Jaffe CA, Barkan AL. Treatment of acromegaly with dopamine agonists. Endocrinol Metab Clin North Am 1992;21:713-735.
25. Abs R, Verhelst J, Maiter D, Van Acker K, Nobels F, Coolens JL, Mahler C, Beckers A. Cabergoline in the treatment of acromegaly: A study in 64 patients. J Clin Endocrinol Metab 1998;83:374-378
26. Freda PU. Clinical Review: Somatostatin analogs in acromegaly. J Clin Endocrinol Metab 2002;87:3013-3018.
27. Colao A, Ferone D, Marzullo P, Cappabianca P, Cirillo S, Boerlin V, Lancranjan I, Lombardi G. Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly. J Clin Endocrinol Metab 2001;86:2779-2786.
28. Colao A, Marzullo P, Ferone D, Marino V, Pivonello R, Di Somma C, Di Sarno A, Giaccio A, Lombardi G. Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly. J Endocrinol Invest 1999;22:40-47.
29. Burt MG, Ho KK. Comparison of efficacy and tolerability of somatostatin analogs and other therapies for acromegaly. Endocrine. 2003;20:299-305.
30. Barkan AL, Kelch RP, Hopwood J, Beitins IZ. Treatment of acromegaly with long acting SMS 201-995. J Clin Endocrinol Metab 1988;66:16-23.
31. Van der Hoek J, de Herder WW, Feelders RA, van der Lely AJ, Uitterlinden P, Boerlin V, Brans C, Poon KW, Lewis I, Weckbecker G, Krahnke T, Hofland LJ, Lamberts SW. A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients. J Clin Endocrinol Metab 2004;89(2):638-645.
32. Ho PJ, Freiberg RD, Barkan AL. Regulation of pulsatile growth hormone secretion by fasting in normal subjects and patients with acromegaly. J Clin Endocrinol Metab. 1992;75:812-819.
33. Ho KY, Veldhuis JD, Johnson ML, Furlanetto R, Evans WS, Alberti KG, Thorner MO. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. J Clin Invest 1988;81:968-975.
34. Clemmons DR, Underwood LE, Judson J. Van WykJJ. Estradiol treatment of acromegaly. The American Journal of Medicine 1980;69:571-577.
35. McCarthy M. Estrogen agonists/antagonists downregulate GH. Medical Hypotheses 2003;61:335-339.
36. Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RJ, Ho KK. Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc Natl Acad Sci USA 2003;100(3):1016-1021.
37. Attanasio R, Barausse M, Cozzi R. Raloxifene lowers IGF-I levels in acromegalic women. Eur J Endocrinol 2003; 148:443-448.
38. Dimaraki EV, Symons KV, Barkan AL. Raloxifene decreases serum IGF-I in male patients with active acromegaly. Eur J Endoctinol 2004; 150:481-497.
39. 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.
40. 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.
41. Kopchick JJ, Okada S. GH receptor antagonists: Discovery and potential uses. Growth Harm IGF-1 Res 2001; (Suppl A):S103-S109.
42. Okada S, Kopchick JJ. Biological effects of GH and its antagonist. Trends in Molecular Medicine 2001;7:126-132.
43. 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.
44. Drake WM, Parkinson C, Besser GM, Trainer PJ. Clinical use of GH receptor antagonist in treatment of acromegaly. Trends Endocrinol and Metab 2001;12:408-413.
45. Stewart PM. Pegvisomant: An advance in clinical efficacy in acromegaly. Eur J Endocrinol 2003;148(Suppl 2):S27-S32.
46. 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.
47. 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(9295):1754-1759.
48. Trainer PJ, Drake WM, Perry LA, Taylor NF, Besser GM, Monson JP. Modulation of cortisol metabolism by the growth hormone receptor antagonist pegvisomant in patients with acromegaly. J Clin Endocrinol Metab 2001;86(7):2989-2992.
49. Parkinson C, Drake WM, Wieringa G, Yates AP, Besser GM, Trainer PJ. Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly. Clin Endocrinol (Oxf) 2002;56(3):303-311.
50. Veldhuis JD, Bidlingmaier M, Anderson SM, Wu Z, Strasburger CJ. Lowering total plasma insulin-like growth factor I concentrations by way of a novel, potent, and selective growth hormone (GH) receptor antagonist, pegvisomant (B2036-peg), augments the amplitude of GH secretory bursts and elevates basal/nonpulsatile GH release in healthy women and men. J Clin Endocrinol Metab 2001;86(7):3304-3310.
51. Drake WD, Trainer PJ. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol, 2003;149:521-527.
52. Clemmons DR, Chihara K, Freda PU, Ho KK, Klibanski A, Melmed S, Shalet SM, Strasburger CJ, Trainer PJ, Thorner MO. Optimizing control of acromegaly: Integrating a growth hormone receptor antagonist into the treatment algorithm. J Clin Endocrinol Metab 2003;88:4759-4767.
53. Smith L, Schaeffer J. Essential role of GH in Ischemia induced Retinal neovascularization. Science 1997;276:1706-1708.
54. Beck R, Ellis K. The effect of Growth hormone receptor antagonist drug on proliferative diabetic retinopathy. Ophthalmology 2001;108:2266-2272.
55. Landau D, Chin E, Bondy C, Domene H, Roberts CT, Gronbaek H, Flyvberg A, LeRoith D. Expression of Insulin like Growth Factor binding proteins in the rat kidney: Effects of long term diabetes. Endocrinology 1995,136:1835-1842.
56. Chen N, Kopchick JJ. Effects of Streptozotocin treatment in GH and GH antagonist transgenic mice. Endocrinology 1995; 136:660-667.
57. Segev Y, Landau D, Rasch R, Flyvbjerg A, Phillip M. Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice. J Am Soc Nephrol 1999;10:2374-2381.
58. Bengtsson BA, Eden S, Ernest I, Oden A, Sjogren B. Epidemiology and long term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Endocrinol 1988.223:327-335.
59. Barzilay J, Heatley GJ, Gushing GW. Benign and malignant tumors in patients with acromegaly. Arch Intern Med 1991;151:1629-1632.
60. Blakesley VA, Stannard BS, Kalebic T, Helman LJ, LeRoith D. Role of the IGF-I receptor in mutagenesis and tumor promotion. J Endocrinol 1997;152(3):339-344.
61. Ma J, Pollack MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, Stamper MJ. Prospective study of colorectal cancer risk and plasma levels of insulin like growth factor and IGF- binding protein-3. J N Cancer Inst 1999:91:620-625.
62. LeRoith D, Roberts CT Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003;195(2):127-137.
63. Wu Y, Yakar S, Zhao L, Hennighausen L, LeRoith D. Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res 2002;62(4):1030-1035.
64. Furstenberger G, Morant R, Senn HJ. Insulin-like growth factors and breast cancer. Onkologie 2003;26:290-294.
65. Torrisi R, Baglietto L, Johansson H, Veronesi G, Bonanni B, Guerrieri-Gonzaga A, Ballardini B, Decensi A. Effect of raloxifene on IGF-I and IGFBP-3 in postmenopausal women with breast cancer Br J Cancer 2001;85:1838-1841.
66. Pollak M, Blouin MJ, Zhang JC, Kopchick JJ. Reduced mammary gland carcinogenesis in transgenic mice expressing a growth hormone antagonist. Br J Cancer 2001;85:428-430.
67. McCutcheon IE, Flyvbjerg A, Hill H, Li J, Bennett WF, Scarlett JA, Friend KE. Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice. J Neurosurg 2001;94(3):487-492.