Somatostatin receptor ligands and resistance to treatment in pituitary adenomas

Journal of Molecular Endocrinology

Volumn 52, Issue 3, 2014, Pages

  Cuevas Ramos, Daniel ^a   Fleseriu, Maria ^b  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPEPTIN; DG 3173; DOPASTATIN; OCTREOLIN; OCTREOTIDE; PASIREOTIDE; PEGVISOMANT; SOMATOPRIM; SOMATOSTATIN RECEPTOR; UNCLASSIFIED DRUG; BIM 23A760; CORTICOTROPIN; DOPAMINE; HORMONE; HUMAN GROWTH HORMONE; LIGAND; PROLACTIN; PTR 3173; SOMATOSTATIN; THYROTROPIN;

ACTH SECRETING ADENOMA; CANCER GROWTH; CELL MEMBRANE; CUSHING DISEASE; DESENSITIZATION; GROWTH HORMONE SECRETING ADENOMA; GROWTH INHIBITION; HUMAN; HYPOPHYSIS ADENOMA; HYPOPHYSIS TUMOR; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; ADENOMA; ANALOGS AND DERIVATIVES; APOPTOSIS; BIOSYNTHESIS; CELL CYCLE CHECKPOINT; DRUG RESISTANCE; GENETICS; METABOLISM; PHYSIOLOGY; PITUITARY NEOPLASMS; SECRETION (PROCESS); SIGNAL TRANSDUCTION;

ADENOMA; ADRENOCORTICOTROPIC HORMONE; APOPTOSIS; CELL CYCLE CHECKPOINTS; DOPAMINE; DRUG RESISTANCE, NEOPLASM; HORMONES; HUMAN GROWTH HORMONE; HUMANS; LIGANDS; PITUITARY NEOPLASMS; PROLACTIN; RECEPTORS, SOMATOSTATIN; SIGNAL TRANSDUCTION; SOMATOSTATIN; THYROTROPIN;

EID: 84901378453     PISSN: 09525041     EISSN: 14796813     Source Type: Journal    
DOI: 10.1530/JME-14-0011     Document Type: Review

References (105)

1. Alberti K. G, Christensen NJ, Christensen SE, Hansen AP, Iversen J, Lundbaek K., Seyer-Hansen K & Orskov H 1973 Inhibition of insulin secretion by somatostatin. Lancet 2 1299-1301. (doi:10.1016/S0140-6736(73)92873-0)
2. Asa S. L, Digiovanni R, Jiang J, Ward ML, Loesch K, Yamada S, Sano T, Yoshimoto K., Frank SJ & Ezzat S 2007 A growth hormone receptor mutation impairs growth hormone autofeedback signaling in pituitary tumors. Cancer Research 67 7505-7511. (doi:10.1158/0008-5472.CAN-07-0219)
3. Ballare E., Parsani L, Lania AG, Filopanti M, Giammona E, Corbetta S, Mantovani S., Arosio M, Beck-Peccoz P, Faglia G et al. 2001 Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment. Journal of Clinical Endocrinology and Metabolism 86 3809-3814. (doi:10.1210/jcem.86.8.7787)
4. Bauer W., Briner U, Doepfner W, Haller R, Huguenin R, Marbach P, Petcher T. J & Pless 1982 SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sciences 31 1133-1140. (doi:10.1016/0024-3205(82)90087-X)
5. Benali N., Cordelier P, Calise D, Pages P, Rochaix P, Nagy A, Esteve JP, Pour P. M, Schally AV, Vaysse N et al. 2000 Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238. PNAS 97 9180-9185. (doi:10.1073/pnas.130196697)
6. Ben-Shlomo A. & Melmed S 2008 Somatostatin agonist for treatment of acromegaly. Molecular and Cellular Endocrinology 286 192-198. (doi:10.1016/j.mce.2007.11.024)
7. Ben-Shlomo A. & Melmed S 2010 Pituitary somatostatin receptor signaling. Trends in Endocrinology and Metabolism 21 123-133. (doi:10.1016/j.tem. 2009.12.003)
8. Ben-Shlomo A., Schmid H, Wawrowsky K, Pichurin O, Hubina E, Chesnokova V., Liu NA, Culler M & Melmed S 2009 Differential ligand-mediated pituitary somatostatin receptor subtype signaling: implications for corticotroph tumor therapy. Journal of Clinical Endocrinology and Metabolism 94 4342-4350. (doi:10.1210/jc. 2009-1311)
9. Ben-Shlomo A., Pichurin O, Khalafi R, Zhou C, Chesnokova V, Ren SG, Liu N. A & Melmed S 2013 Constitutive somatostatin receptor subtype 2 activity attenuates GH synthesis. Endocrinology 154 2399-2409. (doi:10.1210/en.2013-1132)
10. Biller B. M, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M., Colao A, Hermus AR, Hofland LJ et al. 2008 Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. Journal of Clinical Endocrinology and Metabolism 93 2454-2462. (doi:10.1210/jc.2007-2734)
11. Biller M. B, Petersenn S, Pivonello R, Findling J, Fleseriu M, Trovato A, Hughes G., Ligueros-Saylan M & Newell-Price J 2013 Evaluation of latenight salivary cortisol during 12 months of pasireotide treatment in patients with Cushing's disease. Endocrine Reviews 34 (03_Meeting-Abstracts): MON-89.
12. Boden G., Ryan IG, Eisenschmid BL, Shelmet JJ & Owen OE 1986 Treatment of inoperable glucagonoma with the long-acting somatostatin analogue SMS 201-995. New England Journal of Medicine 314 1686-1689. (doi:10.1056/NEJM198606263142606)
13. Boscaro M., Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P., Tabarin A, Biller BM, Findling J et al. 2009 Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. Journal of Clinical Endocrinology and Metabolism 94 115-122. (doi:10.1210/jc.2008-1008)
14. Boscaro M., Bertherat J, Findling J, Fleseriu M, Atkinson AB, Petersenn S, Schopohl J., Snyder P, Hughes G, Trovato A et al. 2013 Extended treatment of Cushing's disease with pasireotide: results from a 2-year, phase II study. Pituitary [in press]. (doi:10.1007/s11102-013-0503-3)
15. Brazeau P., Vale W, Burgus R, Ling N, Nutcher M, Rivier J & Guillemin R Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179 77-79. (doi:10. 1126/science.179.4068.77)
16. Bronstein M., Sheppard M, Freda P, Gu F, Shen C, Gadleha M, Fleseriu M, Hermosillo Resendiz K., Ruffin M, Chen Y et al. 2012 Pasireotide LAR is significantly more effective than octreotide LAR at providing biochemical control in patients with acromegaly: results of a 12-month randomized, double-blind, multicenter, phase III study. Endocrine Reviews 33 OR49-OR43.
17. de Bruin C., Feelders RA, Waaijers AM, van Koetsveld PM, Sprij-Mooij DM, Lamberts S. W & Hofland LJ 2009 Differential regulation of human dopamine D2 and somatostatin receptor subtype expression by glucocorticoids in vitro. Journal of Molecular Endocrinology 42 47-56. (doi:10.1677/JME-08-0110)
18. Bruns C., Lewis I, Briner U, Meno-Tetang G & Weckbecker G 2002 SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. European Journal of Endocrinology 146 707-716. (doi:10.1530/eje. 0.1460707)
19. Brzana J., Yedinak CG, Gultekin SH, Delashaw JB & FleseriuM2013 Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary 16 490-498. (doi:10.1007/s11102-012-0445-1)
20. Casarini A. P, Jallad RS, Pinto EM, Soares IC, Nonogaki S, Giannella-Neto D, Musolino N. R, Alves VA & Bronstein MD 2009 Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment. Pituitary 12 297-303. (doi:10.1007/s11102-009-0175-1)
21. Castillo V., Theodoropoulou M, Stalla J, Gallelli MF, Cabrera-Blatter MF, Haedo M. R, Labeur M, Schmid HA, Stalla GK & Arzt E 2011 Effect of SOM230 (pasireotide) on corticotroph cells: action in dogs with Cushing's disease. Neuroendocrinology 94 124-136. (doi:10.1159/ 000327429)
22. Colao A., Auriemma RS, Lombardi G & Pivonello R 2011 Resistance to somatostatin analogs in acromegaly. Endocrine Reviews 32 247-271. (doi:10.1210/er.2010-0002)
23. Colao A., Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U., Mills D, Salgado LR & Biller BM 2012 A 12-month phase 3 study of pasireotide in Cushing's disease. New England Journal of Medicine 366 914-924. (doi:10.1056/NEJMoa1105743)
24. Cordelier P., Estéve JP, Bousquet C, Delesque N, O'Carroll AM, Schally AV, Vaysse N., Susini C & Buscail L 1997 Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. PNAS 94 9343-9348. (doi:10.1073/pnas.94.17.9343)
25. Córdoba-Chacón J., Gahete MD, Durán-Prado M, Pozo-Salas AI, Malagón M. M, Garci{dotless}á-Navarro F, Kineman RD, Luque RM & Castanõ JP Identification and characterization of new functional truncated variants of somatostatin receptor subtype 5 in rodents. Cellular and Molecular Life Sciences 67 1147-1163. (doi:10.1007/ s00018-009-0240-y)
26. Córdoba-Chacón J., Gahete MD, Culler MD, Castanõ JP, Kineman RD & Luque R. M 2012a Somatostatin dramatically stimulates growth hormone release from primate somatototrophs acting at low doses via somatostatin receptor 5 and cyclic AMP. Journal of Neuroendocrinology 24 453-463. (doi:10.1111/j.1365-2826.2011.02261.x)
27. Córdoba-Chacón J., Gahete MD, Castanõ JP, Kineman RD & Luque RM 2012b Homologous and heterologous in vitro regulation of pituitary receptors for somatostatin, growth hormone (GH)-releasing hormone, and ghrelin in a nonhuman primate (Papio anubis). Endocrinology 153 264-272. (doi:10.1210/en.2011-1677)
28. Durán-Prado M., Genete MD, Martínez-Fuentes AJ, Luque RM, Quintero A, Webb S. M, Benito-Lopez P, Leal A, Shulz S, Garcia-Navarro F et al. 2009 Identification and characterization of two novel truncated but functional isoforms of the somatostatin receptor subtype 5 differentially present in pituitary tumors. Journal of Clinical Endocrinology and Metabolism 94 2634-2643. (doi:10.1210/jc.2008-2564)
29. Fedele M., De Martino I, Pivonello R, Ciarmiello A, Del Basso De Caro ML, Visone R., Palmieri D, Pierantoni GM, Arra C, Schmid HA et al. 2007 SOM230, a new somatostatin analogue, is highly effective in the therapy of growth hormone/prolactin-secreting pituitary adenomas. Clinical Cancer Research 13 2738-2744. (doi:10.1158/1078-0432.CCR-06-2505)
30. Fleseriu M. 2011 Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review. Pituitary 14 184-193. (doi:10.1007/s11102-010-0282-z)
31. Fleseriu M. 2012 Medical management of persistent and recurrent Cushing disease. Neurosurgery Clinics of North America 23 653-668. (doi:10.1016/ j.nec.2012.06.012)
32. Fleseriu M. 2013 The role of combination medical therapy in acromegaly: hope for the nonresponsive patient. Current Opinion in Endocrinology, Diabetes, and Obesity 20 321-329.
33. Fleseriu M. & Petersenn S 2012 Medical management of Cushing's disease: what is the future? Pituitary 15 330-341. (doi:10.1007/s11102-012-0397-5)
34. Fleseriu M. & Petersenn S 2013 New avenues in the medical treatment of Cushing's disease: corticotroph tumor targeted therapy. Journal of Neuro-Oncology 114 1-11. (doi:10.1007/s11060-013-1151-1)
35. Fleseriu M., Sheppard M, Bronstein M, Freda P, Gu F, Shen C, Gadleha M, Hermosillo R., Ruffin M, Chen Y et al. 2012 Pasireotide LAR vs octreotide LAR in patients with acromegaly: double-blind, crossover, extension period to a randomized, double-blind, multicenter, phase III study. Endocrine Abstracts 29 1404.
36. Florio T. 2008 Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors. Frontiers in Bioscience 13 822-840. (doi:10.2741/2722)
37. Florio T., Morini M, Villa V, Arena S, Corsaro A, Thellung S, Culler MD, Pfeffer U., Noonan DM, Schettini G et al. 2003 Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology 144 1574-1584. (doi:10.1210/ en.2002-220949)
38. Fougner S. L, Bollerslev J, Latif F, Haid JK, Lund T, Ramm-Pettersen J & Berg J. P 2008 Low levels of raf kinase inhibitory protein in growth hormone-secreting pituitary adenomas correlate with poor response to octreotide treatment. Journal of Clinical Endocrinology and Metabolism 93 1211-1216. (doi:10.1210/jc.2007-2272)
39. Fougner S. L, Lekva T, Borota OC, Hald JK, Bollerslev J & Berg JP 2010 The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response. Journal of Clinical Endocrinology and Metabolism 95 2334-2342. (doi:10.1210/jc.2009-2197)
40. Gadelha M. R, Kasuki L & KorbonitsM 2013 Novel pathway for somatostatin analogs in patients with acromegaly. Trends in Endocrinology and Metabolism 24 238-246. (doi:10.1016/j.tem.2012.11.007)
41. Gatto F., Barbieri F, Gatti M, Wurth R, Schulz S, Ravetti JL, Zona G, Culler M. D, Saveanu A, Giusti M et al. 2012 Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins. Clinical Endocrinology 76 407-414. (doi:10.1111/j.1365-2265.2011.04200.x)
42. Gatto F., Feelders R, van der Pas R, Kros JM, Dogan F, Koetsveld PM, van der Lelij A. J, Neggers SJ, Minuto F, de HerderWet al. 2013 b-arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly. Endocrinology 154 4715-4725. (doi:10.1210/en.2013-1672)
43. Giustina A., Bonadonna S, Bugari G, Colao A, Cozzi R, Cannavo S, De Marinis L., Degli Uberti E, Bogazzi F, Mazziotti G et al. 2009 High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. European Journal of Endocrinology 331-338. (doi:10.1530/EJE-09-0372)
44. Giustina A., Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva F. F, Trainer P, Ghigo E, Ho K & Melmed S 2010 A consensus on criteria for cure of acromegaly. Journal of Clinical Endocrinology and Metabolism 95 3141-3148. (doi:10.1210/jc.2009-2670)
45. Giustina A., Mazziotti G, Torri V, Spinello M, Floriani I & Melmed S 2012 Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS ONE 7 e36411. (doi:10.1371/journal.pone.0036411)
46. Giustina A., Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A., van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK et al. Expert consensus document: a consensus on the medical treatment of acromegaly. Nature Reviews. Endocrinology 10 243-248. (doi:10.1038/nrendo.2014.21)
47. van Hagen P. M, Krenning EP, Kwekkeboom DJ, Reubi JC, Anker-Lugtenburg PJ, Löwenberg B & Lamberts SW 1994 Somatosatin and the immune and hematopoetic system; a review. European Journal of Clinical Investigation 24 91-99. (doi:10.1111/j.1365-2362. 1994.tb00972.x)
48. Hameed N., Yedinak CG, Brzana J, Guitekin SH, Coppa ND, Dogan A, Delashaw J. B & Fleseriu M 2013 Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing's disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience. Pituitary 16 452-458. (doi:10.1007/ s11102-012-0455-z)
49. Heck A., RingstadG, Fougner SL, Casar-BorotaO, Nome T, Ramm-Pettersen J & Bollersiev J 2012 Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clinical Endocrinology 77 72-78. (doi:10.1111/j.1365-2265.2011.04286.x)
50. Hofland L. J & Lamberts SW 2003 The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocrine Reviews 24 28-47. (doi:10.1210/er.2000-0001)
51. Hofland L. J, van der Hoek J, van Koetsveld PM, de Herder WW, Waaijers M, Sprij-Mooij D., Bruns C, Weckbecker G, Feelders R, van der Lely AJ et al. The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone-and prolactin-secreting pituitary adenomas in vitro. Journal of Clinical Endocrinology and Metabolism 89 1577-1585. (doi:10.1210/jc.2003-031344)
52. Hofland L. J, van der Hoek J, Feelders R, van Aken MO, van Koetsveld PM, Waaijers M., Sprij Mooij D, Bruns C, Weckbecker G, de HerderWWet al. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. European Journal of Endocrinology 152 645-654. (doi:10.1530/eje.1.01876)c
53. Jaquet P., Ouafik L, Saveanu A, Gunz G, Fina F, Dufour H, Culler MD, Moreau J. P & Enjalbert A 1999 Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas. Journal of Clinical Endocrinology and Metabolism 84 3268-3276.
54. Jaquet P., Saveanu A, Gunz G, Fina F, Zamora AJ, Grino M, Culler MD, Moreau J. P, Enjalbert A & Ouafik LH 2000 Human somatostatin receptor subtypes in acromegaly: distinct patterns ofmessenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypes. Journal of Clinical Endocrinology and Metabolism 85 781-792.
55. Kaupmann K., Bruns C, Raulf F, Weber HP, Mattes H & Lübbert H 1995 Two amino acids, located in transmembrane domains IV and VII, determine the selectivity of the peptide agonist SMS 201-995 for the SSTR2 somatostatin receptor. EMBO Journal 14 727.
56. Koerker D. J, Ruch W, Chideckel E, Palmer J, Goodner CJ, Ensinck J & Gale C. C 1974 Somatostatin: hypothalamic inhibitor of the endocrine pancreas. Science 184 482-484. (doi:10.1126/science.184.4135.482)
57. Lamberts S. W 1988 The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors. Endocrine Reviews 9 17-36. (doi:10.1210/ edrv-9-4-417)
58. Lania A., Mantovani G & Spada A 2008 Genetic abnormalities of somatostatin receptors in pituitary tumors. Molecular and Cellular Endocrinology 286 180-186. (doi:10.1016/j.mce.2007.08.013)
59. Lesche S., Lehmann D, Nagel F, Schmid HA & Schulz S 2009 Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. Journal of Clinical Endocrinology and Metabolism 94 654-661. (doi:10.1210/jc.2008-1919)
60. Lopez F., Esteve JP, Buscali L, Delesqu N, Saint-Laurent N, Théveniau M, Nahmias C., Vaysse N & Susini C 1997 The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. Journal of Biological Chemistry 272 24448-24454. (doi:10.1074/jbc.272.39.24448)
61. Matrone C., Pivonello R, Colao A, Cappabianca P, Cavalo LM, Del Basso De Caro ML, Taylor JE, Culler MD, Lombardi G, Di Renzo GF et al. 2004 Expression and function of somatostatin receptor subtype 1 in human growth hormone secreting pituitary tumors deriving from patients partially responsive or resistant to long-term treatment with somatostatin analogs. Neuroendocrinology 79 142-148. (doi:10.1159/ 000077272)
62. Mazziotti G. & Giustina A 2010 Effects of lanreotide SR and autogel on tumor mass in patients with acromegaly: a systematic review. Pituitary 13 60-67. (doi:10.1007/s11102-009-0169-z)
63. Melmed S. 2006 Medical progress: acromegaly. New England Journal of Medicine 355 2558-2573. (doi:10.1056/NEJMra062453)
64. Melmed S. 2009 Acromegaly pathogenesis and treatment. Journal of Clinical Investigation 119 3189-3202. (doi:10.1172/JCI39375)
65. Melmed S., Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D., Chanson P, Laws E, Schlechte J et al. 2009 Guidelines for acromegaly management: an update. Journal of Clinical Endocrinology and Metabolism 94 1509-1517. (doi:10.1210/jc.2008-2421)
66. Melmed S., Cook D, Schopohi J, GothMI, Lam KS &Marek J 2010 Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension. Pituitary 13 18-28. (doi:10.1007/ s11102-009-0191-1)
67. Mercado M., Borges F, Bouterfa H, Chang TC, Chervin A, Farrall AJ, Patocs A, Petersenn S., Podoba J, Safari M et al. 2007 A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clinical Endocrinology 66 859-868. (doi:10.1111/ j.1365-2265.2007.02825.x)
68. Miller G. M, Alexander JM, Bikkal HA, Katznelson L, Zervas NT & Klibanski A Somatostatin receptor subtype gene expression in pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 80 1386-1392.
69. Murray R. D & Melmed S 2008 A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. Journal of Clinical Endocrinology and Metabolism 93 2957-2968. (doi:10.1210/jc. 2008-0027)
70. Murray R. D, Kim K, Ren SG, Chelly M, Umehara Y &Melmed S 2004 Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. Journal of Clinical Investigation 114 349-356. (doi:10.1172/ JCI19933)
71. Nagel F., Doll C, Pöll F, Kliewer A, Shröder H & Schulz S 2011 Structural determinants of agonist-selective signaling at the sst(2A) somatostatin receptor. Molecular Endocrinology 25 859-866. (doi:10.1210/me.2010-0407)
72. Nielsen S., Mellemkjaer S, Rasmussen LM, Ledet T, Olsen N, Bojsen-Moller M., Astrup J, Weeke J & Jorgensen JO 2001 Expression of somatostatin receptors on human pituitary adenomas in vivo and ex vivo. Journal of Endocrinological Investigation 24 430-437.
73. Pan M. G, Florio T & Stork PJ 1992 G protein activation of a hormonestimulated phosphatase in human tumor cells. Science 256 1215-1217. (doi:10.1126/science.256.5060.1215)
74. van der Pas R, Feelders RA, Gatto F, de Bruin C, Pereira AM, van Koetsveld P. M, Sprij Mooij DM, Waaijers AM, Dogan F, Schulz S et al. 2013 Preoperative normalization of cortisol levels in Cushing's disease after medical treatment: consequences for somatostatin and dopamine receptor subtype expression and in vitro response to somatostatin analogs and dopamine agonists. Journal of Clinical Endocrinology and Metabolism 98 E1880-E1890. (doi:10.1210/ jc.2013-1987)
75. Patel Y. C, Greenwood MT, Kent G, Panetta R & Srikant CB 1993 Multiple gene transcripts of the somatostatin receptor SSTR2: tissue active distribution and cAMP regulation. Biochemical and Biophysical Research Communications 192 288-294. (doi:10.1006/bbrc.1993.1412)
76. Patel Y. C, Greenwood MT, Warszynska A, Panetta R & Srikant CB 1994 All five cloned human somatostatin receptors (hSSTR1-5) are functionally coupled to adenylyl cyclase. Biochemical and Biophysical Research Communications 198 605-612. (doi:10.1006/bbrc.1994.1088)
77. Petersenn S., Schopohl J, Barkan A, Mohideen P, Colao A, Abs R, Buchelt A, Ho Y. Y, Hu K, Farrall AJ et al. 2010 Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. Journal of Clinical Endocrinology and Metabolism 95 2781-2789. (doi:10.1210/jc.2009-2272)
78. Plöckinger U., Hoffmann U, Geese M, Lupp A, Buchfelder M, Flitsch J, Vajkoczy P., Jakob W, Saeger W, Schulz S et al. 2012 DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4-and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours. European Journal of Endocrinology 166 223-234. (doi:10.1530/ EJE-11-0737)
79. Reisine T. & Bell GI 1995 Molecular biology of somatostatin receptors. Endocrine Reviews 16 427.
80. Ren S. G, Kim S, Taylor J, Dong J, Moreau JP, Culler MD & Melmed S 2003a Suppression of rat and human growth hormone and prolactin secretion by a novel somatostatin/dopaminergicchimeric ligand. Journal of Clinical Endocrinology and Metabolism 88 5414-5421. (doi:10.1210/jc. 2003-030302)
81. Ren S. G, Taylor J, Dong J, Yu R, Culler MD & Melmed S 2003b Functional association of somatostatin receptor subtypes 2 and 5 in inhibiting human growth hormone secretion. Journal of Clinical Endocrinology and Metabolism 88 4239-4245. (doi:10.1210/jc.2003-030303)
82. Reubi J. C, Schaer JC, Waser B & Mengod G 1994 Expression and localization of somatostatin receptor SSTR1, SSTR2, and SSTR3 messenger RNAs in primary human tumors using in situ hybridization. Cancer Research 54 3455-3459.
83. Reubi J. C, Waser B, Schaer JC & Laissue JA 2001 Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. European Journal of Nuclear Medicine 28 836-846. (doi:10.1007/s002590100541)
84. Richardson U. I & Schonbrunn A 1981 Inhibition of adrenocorticotropin secretion by somatostatin in pituitary cells in culture. Endocrinology 108 281-290. (doi:10.1210/endo-108-1-281)
85. Rocheville M., Lange DC, Kumar U, Sasi R, Patel RC & Patel YC 2000 Subtypes of the somatostatin receptor assemble as functional homo-and heterodimers. Journal of Biological Chemistry 275 7862. (doi:10.1074/jbc.275.11.7862)
86. Sellers L. A, Alderton F, Carruthers AM, Schindler M & Humphrey PP 2000 Receptor isoforms mediate opposing proliferative effects through betagamma-activated p38 or Akt pathways. Molecular and Cellular Biology 20 5974-5985. (doi:10.1128/MCB.20.16.5974-5985.2000)
87. Shimon I. 2003 Somatostatin receptors in pituitary and development of somatostatin receptor subtype-selective analogs. Endocrine 20 265-269. (doi:10.1385/ENDO:20:3:265)
88. Shimon I., Tylor JE, Dong JZ, Bitonte RA, Kim S, Morgan B, Coy DH, Culler M. D &Melmed S 1997a Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. Journal of Clinical Investigation 99 789-798. (doi:10.1172/ JCI119225)
89. Shimon I., Yan X, Taylor JE, Weiss MH, Culler MD & Melmed S 1997b Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. Journal of Clinical Investigation 100 2386-2392. (doi:10.1172/ JCI119779)
90. Siler T. M, Yen SC, Vale W & Guillemin R 1974 Inhibition by somatostatin on the release of TSH induced in man by thyrotropin-releasing factor. Journal of Clinical Endocrinology and Metabolism 38 742-745. (doi:10.1210/jcem-38-5-742)
91. Strnad J. & Hadcock JR 1995 Identification of a critical aspartate residue in transmembrane domain three necessary for the binding of somatostatin to the somatostatin receptor SSTR2. Biochemical and Biophysical Research Communications 216 913. (doi:10.1006/bbrc.1995.2708)
92. Taboada G. F, Luque RM, Bastos W, Guimaräes RF, Marcondes JB, Chimelli L. M, Fontes R, Mata PJ, Filho PN, Carvalho DP et al. 2007 Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas. European Journal of Endocrinology 156 65-74. (doi:10.1530/ eje.1.02313)
93. Taboada G. F, Luque RM, Neto LV, Machado E de O, Sbaffi BC, Domingues R. C, Marcondes JB, Chimelli LM, Fontes R, Niemeyer P et al. Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. European Journal of Endocrinology 158 295-303. (doi:10.1530/ EJE-07-0562)
94. Taylor J. E, Bogden AE, Moreau JP & Coy DH 1988 In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue. Biochemical and Biophysical Research Communications 81-86. (doi:10.1016/S0006-291X(88)81192-6)
95. Theodoropoulou M., Stalla GK & Spengler D 2010 ZAC1 target genes and pituitary tumorigenesis. Molecular and Cellular Endocrinology 326 60-65. (doi:10.1016/j.mce.2010.01.033)
96. Tritos N. A & Biller BM 2013 Medical management of Cushing's disease. Journal of Neuro-Oncology [in press]. (doi:10.1007/s11060-013-1269-1)
97. Tuvia S., Atsmon J, Teichman SL, Katz S, Salama P, Pelled D, Landau I, Karmell I., Bidlingmaler M, Strasburger CJ et al. 2012 Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. Journal of Clinical Endocrinology and Metabolism 97 2362-2369. (doi:10.1210/jc.2012-1179)
98. Vale W., Rivier C, Brazeau P & Guillemin R 1974 Effects of somatostatin on the secretion by thyrotropin and prolactin. Endocrinology 95 968-977. (doi:10.1210/endo-95-4-968)
99. Vieira Neto L., Machado E de O, Luque RM, Taboada GF, Marcondes JB, Chimelli L. M, Quintella LP, Niemeyer P Jr, de Carvalho DP, Kineman RD et al. 2009 Expression analysis of dopamine receptor subtypes in normal human pituitaries, nonfunctioning pituitaryadenomas and somatotropinomas, and the association between dopamine and somatostatin receptors with clinical response to octreotide-LAR in acromegaly. Journal of Clinical Endocrinology and Metabolism 94 1931-1937. (doi:10.1210/jc.2008-1826)
100. Vieira Neto L., Wildemberg LE, Colli LM, Kasuki L, Marques NV, Moraes AB, Gasparetto E. L, Takiya CM, Castro M & Gadelha MR 2013 ZAC1 and SSTR2 are downregulated in non-functioning pituitary adenomas but not in somatotropinomas. PLoS ONE 8 e77406. (doi:10.1371/journal. pone.0077406)
101. Wilkinson G. F, FeniukW& Humphrey PP 1997 Characterization of human recombinant somatostatin sst5 receptors mediating activation of phosphoinositide metabolism. British Journal of Pharmacology 121 91-96. (doi:10.1038/sj.bjp.0701116)
102. Yoshihara A., Isozaki O, Hizuka N, Nozoe Y, Harada C, Ono M, Kawamata T, Kubo O., Hori T & Takano K 2007 Expression of type 5 somatostatin receptor in TSH-secreting pituitary adenomas: a possible marker for predicting long-term response to octreotide therapy. Endocrine Journal 54 133-138. (doi:10.1507/endocrj.K06-133)
103. Zatelli M. C, Piccin D, Tagliati F, Ambrosio MR, Margutti A, Padovani R, Scanarini M., Culler MD & degli Uberti EC 2003 Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)-and prolactin (PRL)-secreting pituitary adenomas: effects on cell viability, GH, and PRL secretion. Journal of Clinical Endocrinology and Metabolism 88 2797-2802. (doi:10.1210/jc.2002-021825)
104. Zatelli M. C, Piccin D, Bottoni A, Ambrosio MR, Margutti A, Padavani R, Scanarini M., Taylor JE, Culler MD, Cavazzini L et al. 2004 Evidence for differential effects of selective somatostatin receptor subtype agonists on a-subunit and chromogranin a secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro. Journal of Clinical Endocrinology and Metabolism 89 5181-5188. (doi:10.1210/jc.2003-031954)
105. Zatelli M. C, Piccin D, Vignali C, Tagliati F, Ambrosio MR, Bondanelli M, Cimino V., Bianchi A, Schmid HA, Scanarini M et al. 2007 Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocrine-Related Cancer 14 91-102. (doi:10.1677/ERC-06-0026)