Biomedical papers, 2016 (vol. 160), issue 2

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(2):238-243 | 10.5507/bp.2015.058

Expression profiles of somatostatin, dopamine, and estrogen receptors in pituitary adenomas determined by means of synthetic multilocus calibrators

Monika Drastikovaa, Martin Beraneka,b, Filip Gabalecc, David Netukad, Vaclav Masopustd, Tomas Cesake, Josef Marekf, Vladimir Palickaa, Jan Capc
a Institute of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic
b Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague
c 4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove
d Department of Neurosurgery, 1st Faculty of Medicine, Charles University in Prague and Central Military Hospital Prague
e Department of Neurosurgery, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove
f 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague

Aims: Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA.

Methods: Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene.

Results: The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA.

Conclusion: We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment.

Keywords: pituitary adenoma, somatostatin receptor, dopamine receptor, estrogen receptor, real-time PCR, gene expression

Received: June 23, 2015; Accepted: November 11, 2015; Prepublished online: November 24, 2015; Published: June 24, 2016


References

  1. Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab 2008;93:3717-26. Go to original source... Go to PubMed...
  2. Losa M, Mortini P, Barzaghi R, Ribotto P, Terreni MR, Marzoli SB, Pieralli S, Giovanelli M. Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence. J Neurosurg 2008;108:525-32. Go to original source... Go to PubMed...
  3. Cakir M., Dworakowska D, Grossman A. Somatostatin receptor biology in neuroendocrine and pituitary tumours: part 1 - molecular pathways. J Cell Mol Med 2010;14:2570-84. Go to original source... Go to PubMed...
  4. Reubi JC, Laissue J, Krenning E, Lamberts SW. Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J Steroid Biochem Mol Biol 1992;43:27-35. Go to original source... Go to PubMed...
  5. Cakir M., Dworakowska D, Grossman A. Somatostatin receptor biology in neuroendocrine and pituitary tumours: part 2 - clinical implications. J Cell Mol Med 2010;14:2585-91. Go to original source... Go to PubMed...
  6. Taboada GF, Luque RM, Bastos W, Guimarães RF, Marcondes JB, Chimelli LM, Fontes R, Mata PJ, Filho PN, Carvalho DP, Kineman RD, Gadelha MR. Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas. Eur J Endocrinol 2007;156:65-74. Go to original source... Go to PubMed...
  7. Nishioka H, Tamura K, Iida H, Kutsukake M, Endo A, Ikeda Y, Haraoka J. Co-expression of somatostatin receptor subtypes and estrogen receptor-α mRNAs by non-functioning pituitary adenomas in young patients. Mol Cell Endocrinol 2011;331:73-8. Go to original source... Go to PubMed...
  8. Visser-Wisselaar HA, Van Uffelen CJ, Van Koetsveld PM, Lichtenauer-Kaligis EG, Waaijers AM, Uitterlinden P, Mooy DM, Lamberts SW, Hofland LJ. 17-beta-estradiol-dependent regulation of somatostatin receptor subtype expression in the 7315b prolactin secreting rat pituitary tumor in vitro and in vivo. Endocrinology 1997;138:1180-9. Go to original source... Go to PubMed...
  9. Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999;20:157-98. Go to original source... Go to PubMed...
  10. O'Toole D, Saveanu A, Couvelard A, Gunz G, Enjalbert A, Jaquet P, Ruszniewski P, Barlier A. The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies. Eur J Endocrinol 2006;155:849-57. Go to original source... Go to PubMed...
  11. Korner M, Waser B, Schonbrunn A, Perren A, Reubi JC. Somatostatin receptor subtype 2A immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting. Am J Surg Pathol 2012;36:242-52. Go to original source... Go to PubMed...
  12. Pisarek H, Kunert-Radek J, Radek M, Swietoslawski J, Winczyk K, Pawlikowski M. Expression of somatostatin receptor subtypes in primary and recurrent gonadotropinomas: are somatostatin receptors involved in pituitary adenoma recurrence? Neuro Endocrinol Lett 2011;32:96-101. Go to PubMed...
  13. Peineau S, Guimiot F, Csaba Z, Jacquier S, Fafouri A, Schwendimann L, de Roux N, Schulz S, Gressens P, Auvin S, Dournaud P. Somatostatin receptors type 2 and 5 expression and localization during human pituitary development. Endocrinology 2014;155:33-9. Go to original source... Go to PubMed...
  14. Waser B, Cescato R, Liu Q, Kao YJ, Körner M, Christ E, Schonbrunn A, Reubi JC. Phosphorylation of sst2 receptors in neuroendocrine tumors after octreotide treatment of patients. Am J Pathol 2012;180:1942-9. Go to original source... Go to PubMed...
  15. Gonzalez B, Vargas G, Ramirez C, Asa S, Cheng S, Sandoval C, Mercado M. Cytoplasmic expression of SSTR2 and 5 by immunohistochemistry and by RT/PCR is not associated with the pharmacological response to octreotide. Endocrinol Nutr 2014;61:523-30. Go to original source... Go to PubMed...
  16. Colao A, Pivonello R, Di Somma C, Savastano S, Grasso LF, Lombardi G. Medical therapy of pituitary adenomas: effects on tumor shrinkage. Rev Endocr Metab Disord 2009;10:111-23. Go to original source... Go to PubMed...
  17. Nielsen S, Mellemkjaer S, Rasmussen LM, Ledet T, Olsen N, Bojsen-Moller M, Astrup J, Weeke J, Jorgensen JO. Expression of somatostatin receptors on human pituitary adenomas in vivo and ex vivo. J Endocrinol Invest 2001;24:430-7. Go to original source... Go to PubMed...
  18. Colao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev 2011;32:247-71. Go to original source... Go to PubMed...
  19. Taboada GF, Luque RM, Neto LV, Machado Ede O, Sbaffi BC, Domingues RC, Marcondes JB, Chimelli LM, Fontes R, Niemeyer P, de Carvalho DP, Kineman RD, Gadelha MR. 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. Eur J Endocrinol 2008;158:295-303. Go to original source... Go to PubMed...
  20. Colao A. The importance of presurgical somatostatin analogue therapy in acromegaly. Endokrynol Pol 2007;58:356-60. Go to PubMed...
  21. Djordjijevic D, Zhang J, Priam M, Viollet C, Gourdji D, Kordon C, Epelbaum J. Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory effects on growth hormone and prolactin release in rat pituitary cell cultures. Endocrinology 1998;139:2272-7. Go to original source... Go to PubMed...
  22. Molitch ME. Management of medically refractory prolactinoma. J Neurooncol 2014;117:421-8. Go to original source... Go to PubMed...
  23. de Bruin C, Pereira AM, Feelders RA, Romijn JA, Roelfsema F, Sprij-Mooij DM, van Aken MO, van der Lelij AJ, de Herder WW, Lamberts SW, Hofland LJ. Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas. J Clin Endocrinol Metab 2009;94:1118-24. Go to original source... Go to PubMed...
  24. Pivonello R, Ferone D, de Herder WW, Kros JM, De Caro ML, Arvigo M, Annunziato L, Lombardi G, Colao A, Hofland LJ, Lamberts SW. Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metab 2004;89:2452-62. Go to original source... Go to PubMed...
  25. Boscaro M, Ludlam WH, Atkinson B, Glusman JE, Petersenn S, Reincke M, Snyder P, Tabarin A, Biller BM, Findling J, Melmed S, Darby CH, Hu K, Wang Y, Freda PU, Grossman AB, Frohman LA, Bertherat J Treatment of pituitary dependent Cushing's disease with the multi-receptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial. J Clin Endocrinol Metab 2009;94:115-22. Go to original source... Go to PubMed...
  26. Pivonello R, De Martino MC, Cappabianca P, De Leo M, Faggiano A, Lombardi G, Hofland LJ, Lamberts SW, Colao A. The medical treatment of Cushing's disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab 2009;94:223-30. Go to original source... Go to PubMed...
  27. Greenman Y, Stern N. How should a nonfunctioning pituitary macroadenoma be monitored after debulking surgery? Clin Endocrinol 2009;70:829-32. Go to original source... Go to PubMed...