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DOI: 10.1055/s-2005-921092
Differential Expression of the Human Somatostatin Receptor Subtypes sst1 to sst5 in Various Adrenal Tumors and Normal Adrenal Gland
Publikationsverlauf
Received 7 March 2005
Accepted after revision 9 August 2005
Publikationsdatum:
22. Dezember 2005 (online)
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Abstract
Somatostatin (SRIF) is a widely distributed peptide with growth-inhibiting effects in various tumors. So far, five distinct human SRIF receptor subtypes (sst1 - sst5) have been identified. We investigated expression of the five ssts in various adrenal tumors and in normal adrenal gland. Tissue was obtained from ten pheochromocytomas (PHEOs), nine cortisol-secreting adenomas (CPAs), eleven aldosterone secreting adenomas (APAs) and eight non-functional adenomas (NFAs) after retroperitoneoscopic surgery, and used for RNA extraction. Adrenal tissue surrounding the tumor was available for analysis in twenty-seven cases. Receptor expression was studied by RT-PCR using sst-specific primers and subsequently confirmed by Southern blotting. Expression of all five receptor subtypes was observed in RNA obtained from normal adrenal gland. Furthermore, each receptor subtype was expressed in more than 50 % of all tumors analyzed. No sst5 expression was found in PHEOs, while sst1 was present in nearly all of these tumors. Only a few of the CPAs expressed subtypes sst1 and sst4. Expression of all five subtypes was distributed equally in APAs. No sst4 was found in any of the NFAs. Differential expression of ssts in various adrenal tumors may point to new aspects in the pathogenesis of these adenomas. Furthermore, the presence of specific ssts could expand the diagnostic and therapeutic strategies during management. New subtype specific analogues of SRIF may be used in the future depending on the type of adrenal tumor and receptor subtype expressed.
Key words
Somatostatin receptor - somatostatin analogues - adrenal gland - adrenal tumor - pheochromocytoma - aldosterone - cortisol - expression
References
- 1 Reubi J C, Laissue J A. Multiple actions of somatostatin in neoplastic disease. Trends Pharmacol Sci. 1995; 16 110-115
- 2 Meyerhof W. The elucidation of somatostatin receptor functions: a current view. Rev Physiol Biochem Pharmacol. 1998; 133 55-108
- 3 Bauer W, Briner U, Doepfner W, Haller R, Huguenin R, Marbach P, Petcher T J, Pless J. SMS 201 - 995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci. 1982; 31 1133-1140
- 4 Heiman M L, Murphy W A, Coy D H. Differential binding of somatostatin agonists to somatostatin receptors in brain and adenohypophysis. Neuroendocrinology. 1987; 45 429-436
- 5 Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002; 146 707-716
- 6 Sharma K, Patel Y C, Srikant C B. Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol. 1996; 10 1688-1696
- 7 Panetta R, Patel Y C. Expression of mRNA for all five human somatostatin receptors (hSSTR1-5) in pituitary tumors. Life Sci. 1995; 56 333-342
- 8 Kumar U, Sasi R, Suresh S, Patel A, Thangaraju M, Metrakos P, Patel S C, Patel Y C. Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. Diabetes. 1999; 48 77-85
- 9 Balster D A, O'Dorisio M S, Summers M A, Turman M A. Segmental expression of somatostatin receptor subtypes sst(1) and sst(2) in tubules and glomeruli of human kidney. Am J Physiol Renal Physiol. 2001; 280 F457-F465
- 10 Epelbaum J, Bertherat J, Prevost G, Kordon C, Meyerhof W, Wulfsen I, Richter D, Plouin P F. Molecular and pharmacological characterization of somatostatin receptor subtypes in adrenal, extraadrenal, and malignant pheochromocytomas. J Clin Endocrinol Metab. 1995; 80 1837-1844
- 11 Kimura N, Schindler M, Kasai N, Kimura I. Immunohistochemical localization of somatostatin receptor type 2A in rat and human tissues. Endocr J. 2001; 48 95-102
- 12 Sestini R, Orlando C, Peri A, Tricarico C, Pazzagli M, Serio M, Pagani A, Bussolati G, Granchi S, Maggi M. Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction. Clin Cancer Res. 1996; 2 1757-1765
- 13 Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein S R. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004; 25 309-340
- 14 Koch C A, Pacak K, Chrousos G P. The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors. J Clin Endocrinol Metab. 2002; 87 5367-5384
- 15 Walz M K, Peitgen K, Walz M V, Hoermann R, Saller B, Giebler R M, Jockenhovel F, Philipp T, Broelsch C E, Eigler F W, Mann K. Posterior retroperitoneoscopic adrenalectomy: lessons learned within five years. World J Surg. 2001; 25 728-734
- 16 O'Carroll A M. Localization of messenger ribonucleic acids for somatostatin receptor subtypes (sstr1 - 5) in the rat adrenal gland. J Histochem Cytochem. 2003; 51 55-60
- 17 Zatelli M C, Piccin D, Bondanelli M, Tagliati F, De Carlo E, Culler M D, Uberti E C. An in vivo OctreoScan-negative adrenal pheochromocytoma expresses somatostatin receptors and responds to somatostatin analogs treatment in vitro. Horm Metab Res. 2003; 35 349-354
- 18 Reubi J C, Waser B, Schaer J C, Laissue J A. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001; 28 836-846
- 19 Mundschenk J, Unger N, Schulz S, Hollt V, Steinke R, Lehnert H. Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy. J Clin Endocrinol Metab. 2003; 88 5150-5157
- 20 Unger N, Serdiuk I, Sheu S Y, Walz M K, Schulz S, Schmid K W, Mann K, Petersenn S. Immunohistochemical determination of somatostatin receptor subtypes 1, 2A, 3, 4, and 5 in various adrenal tumors. Endocr Res. 2004; 30 931-934
- 21 Maurea S, Lastoria S, Caraco C, Klain M, Varrella P, Acampa W, Muto P, Salvatore M. The role of radiolabeled somatostatin analogs in adrenal imaging. Nucl Med Biol. 1996; 23 677-680
- 22 van der Harst E, de Herder W W, Bruining H A, Bonjer H J, de Krijger R R, Lamberts S W, van de Meiracker A H, Boomsma F, Stijnen T, Krenning E P, Bosman F T, Kwekkeboom D J. [(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas. J Clin Endocrinol Metab. 2001; 86 685-693
- 23 Boksa P, St-Pierre S, Livett B G. Characterization of substance P and somatostatin receptors on adrenal chromaffin cells using structural analogues. Brain Res. 1982; 245 275-283
- 24 Pisarek H, Pawlikowski M. Immunohistochemical localization of the somatostatin receptor subtype 2A in the rat adrenal gland. Folia Histochem Cytobiol. 2002; 40 27-30
- 25 Rebuffat P, Robba C, Mazzocchi G, Nussdorfer G G. Inhibitory effect of somatostatin on the growth and steroidogenic capacity of rat adrenal zona glomerulosa. J Steroid Biochem. 1984; 21 387-390
- 26 Mazzocchi G, Robba C, Rebuffat P, Gottardo G, Nussdorfer G G. Effect of somatostatin on the zona glomerulosa of rats treated with angiotensin II or captopril: stereology and plasma hormone concentrations. J Steroid Biochem. 1985; 23 353-356
- 27 Reubi J C, Maurer R, von Werder K, Torhorst J, Klijn J G, Lamberts S W. Somatostatin receptors in human endocrine tumors. Cancer Res. 1987; 47 551-558
- 28 Maurer R, Reubi J C. Somatostatin receptors in the adrenal. Mol Cell Endocrinol. 1986; 45 81-90
- 29 Aguilera G, Harwood J P, Catt K J. Somatostatin modulates effects of angiotensin II in adrenal glomerulosa zone. Nature. 1981; 292 262-263
- 30 Boscaro M, Scaroni C, Edwards C R, Mantero F. Inhibitory effect of somatostatin on the aldosterone response to angiotensin II: in vitro studies. J Endocrinol Invest. 1982; 5 173-177
- 31 Jones C R, Millar J A, Lawrie C, Sumner D J, Reid J L. Specific inhibition of aldosterone responses to endogenous and exogenous angiotensin II by somatostatin. Clin Endocrinol (Oxf). 1984; 21 279-284
- 32 Rebuffat P, Mazzocchi G, Gottardo G, Nussdorfer G G. Further studies on the involvement of dopamine and somatostatin in the inhibitory control of the growth and steroidogenic capacity of rat adrenal zona glomerulosa. Exp Clin Endocrinol. 1989; 93 73-81
- 33 Kasprzak A, Rebuffat P, Andreis P G, Mazzocchi G, Nussdorfer G G. Effects of prolonged cysteamine administration on the rat adrenal cortex: evidence that endogenous somatostatin is involved in the control of the growth and steroidogenic capacity of zona glomerulosa. J Steroid Biochem Mol Biol. 1991; 38 469-473
- 34 Mazzocchi G, Malendowicz L K, Meneghelli V, Nussdorfer G G. Evidence that endogenous somatostatin (SRIF) exerts a tonic inhibitory effect on the rat renin-angiotensin-aldosterone system. In Vivo. 1992; 6 9-12
- 35 Rebuffat P, Belloni A S, Musajo F G, Rocco S, Markowska A, Mazzocchi G, Nussdorfer G G. Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF. J Steroid Biochem Mol Biol. 1994; 48 353-360
- 36 Reincke M, Mora P, Beuschlein F, Arlt W, Chrousos G P, Allolio B. Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors: implications for tumorigenesis. J Clin Endocrinol Metab. 1997; 82 3054-3058
- 37 Zwermann O, Beuschlein F, Klink A, Stahl M, Reincke M. The role of the ACTH receptor in adrenal tumors: identification of a novel microsatellite marker. Horm Metab Res. 2004; 36 406-410
- 38 Lin S R, Hsu C H, Tsai J H, Wang J Y, Hsieh T J, Wu C H. Decreased GTPase activity of K-ras mutants deriving from human functional adrenocortical tumours. Br J Cancer. 2000; 82 1035-1040
- 39 Reincke M, Karl M, Travis W H, Mastorakos G, Allolio B, Linehan H M, Chrousos G P. p53 mutations in human adrenocortical neoplasms: immunohistochemical and molecular studies. J Clin Endocrinol Metab. 1994; 78 790-794
- 40 Boulle N, Logie A, Gicquel C, Perin L, Le Bouc Y. Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. J Clin Endocrinol Metab. 1998; 83 1713-1720
- 41 Fottner C, Hoeflich A, Wolf E, Weber M M. Role of the insulin-like growth factor system in adrenocortical growth control and carcinogenesis. Horm Metab Res. 2004; 36 397-405
- 42 Kamio T, Shigematsu K, Sou H, Kawai K, Tsuchiyama H. Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma. Hum Pathol. 1990; 21 277-282
- 43 Peri A, Luciani P, Conforti B, Baglioni-Peri S, Cioppi F, Crescioli C, Ferruzzi P, Gelmini S, Arnaldi G, Nesi G, Serio M, Mantero F, Mannelli M. Variable expression of the transcription factors cAMP response element-binding protein and inducible cAMP early repressor in the normal adrenal cortex and in adrenocortical adenomas and carcinomas. J Clin Endocrinol Metab. 2001; 86 5443-5449
PD Dr. med. Stephan Petersenn
Division of Endocrinology · Medical Center · University of Essen ·
Hufelandstraße 55 · 45122 Essen
Telefon: +49 (201) 723-2822
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eMail: stephan.petersenn@uni-essen.de