Abstract
The small cyclic peptide hormone, somatostatin (ss), is present in the human body in two molecular forms: somatostatin-14 (consisting of 14 amino acids) and somatostatin-28 (28 amino acids). It exerts diverse biologic effects through interaction with specific somatostatin receptors (ssts) in its target tissues. Ss acts as an inhibitor of endocrine and exocrine secretory processes, neurotransmission and as an immune modulation (Lamberts et al., 1996). Ssts belong to the family of G-protein coupled receptors, which characteristically consist of a single polypeptide chain with seven transmembrane spanning domains: extracellular domains with ligand binding sites and intracellular domains with sites linked to the activation of second messengers. At present, five different human sst subtypes (sst1, sst2, sst3, sst4, and sst5) have been cloned and characterised (Patel, 1999). Ssts are encoded by five different genes, each with a distinct chromosomal localization. Although the different sst subtypes are 40% to 60% structurally homologous, each sst subtype mediates different biologic actions of somatostatin. The inhibitory effects of somatostatin or its analogs, mediated via ssts, are linked with several intra-cellular systems: inhibition of adenylyl cyclase, resulting in a decrease in the intracellular cyclic AMP levels; reduction of Ca2+ influxes, resulting in reduced intracellular Ca2+ levels; and, in a number of tissues, stimulation of tyrosine phosphatase activity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Arnold R., Simon B. and Wied M. (2000). Treatment of neuroendocrine GEP tumours with somatostatin analogues: a review. Digestion, 62 (Suppl 1), 84–91.
Beck-Peccoz P., Brucker-Davis R, Persani L., Smallridge R.C. and Weintraub B.D. (1996). Thyrotropin-secreting pituitary tumors. Endocr Rev, 17, 610–638.
Benali N., Ferjoux G., Puente E., Buscail L. and Susini C. (2000a). Somatostatin receptors. Digestion, 62 (Suppl 1), 27–32.
Benali N., Cordelier P., Calise D., Pages P., Rochaix P., Nagy A., Esteve J.P., Pour P.M., Schally A.V., Vaysse N., Susini C. and Buscail L. (2000b). 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. Proc Nat Acad Sei USA, 97, 9180–9185.
Benevento A., Dominioni L., Carcano G. and Dionigi R. (1998). Intraoperative localization of gut endocrine tumors with radiolabeled somatostatin analogs and a gamma-detecting probe. Semin Surg Oncol, 15, 239–244.
Bousquet C., Puente E., Buscail L., Vaysse N. and Susini C. (2001). Antiproliferative effect of somatostatin and analogs. Chemotherapy, 47 (Suppl 2), 30–39.
Bruns C, Lewis I., Briner U., Meno-Tetang G. and Weckbecker G. (2002). SOM230: a new somatostatin peptidomimetic with a broad SRIF receptor binding and a unique inhibitory profile. Eur J Endocrinol, 146, 707–716.
Caplin M.E., Buscombe J.R., Hilson A.J., Jones A.L., Watkinson A.R and Burroughs A.K. (1998) Carcinoid tumour. Lancet, 352, 799–805.
Chanson P., Boerlin V., Ajzenberg C, Bachelot Y., Benito P., Bringer J., Caron P., Charbonnel B., Cortet C, Delemer B., Escobar-Jimenez F., Foubert L., Gaztambide S., Jockenhoevel F., Kuhn J.M., Leclere J., Lorcy Y., Perlemuter L., Prestele H., Roger P., Rohmer V., Santen R., Sassolas G., Scherbaum W.A., Schopohl J., Torres E., Varela C, Villamil R and Webb S.M (2000). Comparison of octreotide acetate LAR and lan-reotide SR in patients with acromegaly. Clin Endocrinol (Oxford), 53, 577–586.
de Herder W.W. and Lamberts S.W.J. (1995). Imaging of pituitary tumours. Baillieres Clin Endocrinol Metabolism, 9, 367–389.
de Herder W.W., van der Lely A.J. and Lamberts S.W.J. (1996). Somatostatin analogue treatment of neuroendocrine tumors. Postgrad Med J, 72, 403–408.
de Herder W.W., Hofland L.J., van der Lely A.J. and Lamberts S.W. (1996). Peptide receptors in gut endocrine tumours. Baillieres Clinical Gastroenterology, 10, 571–587.
de Jong M., Breeman W.A., Bernard B.R, Bakker W.H., Schaar M., van Gameren A., Bugaj J.E., Erion J., Schmidt M., Srinivasan A. and Krenning E.P. (2001). [177Lu-DOTA(o), Tyr3] octreotate for somatostatin receptor-targeted radionuclide therapy. Int J Cancer, 92, 628–633.
Hofland L.J., Breeman W.A., Krenning E.P., de Jong M., Waaijers M., van Koetsveld P.M., Macke H.R. and Lamberts S.W. (1999). Internalization of [DOTA, 125I-Tyr3]Octreotide by somatostatin receptor-positive cells in vitro and in vivo: implications for somatostatin receptor-targeted radio-guided surgery. Proc Assoc Am Physician, 111, 63–69.
Ingle J.N., Suman V.J., Kardinal CG., Krook J.E., Mailliard J.A., Veeder M.H., Loprinzi CL., Dalton R.J., Hartmann L.C., Conover C.A. and Pollak M.N. (1999). A randomized trial of tamoxifen alone or combined with octreotide in the treatment of women with metastatic breast carcinoma. Cancer, 85, 1284–1292.
Jenkins S.A., Kynaston H.G., Davies N.D., Baxter J.N. and Nott D.M. (2001). Somatostatin analogs in oncology: a look to the future. Chemotherapy, 47 (Suppl 2), 162–196.
Krenning E.P., Kwekkeboom D.J., Bakker W.H., Breeman W.A., Kooij P.P., Oei H.Y., van Hagen M., Postema P.T., de Jong M. and Reubi J.C., (1993)- Somatostatin receptor scintigraphy with [111In-DTPA-D-Phei]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med, 20, 716–731.
Krenning E.P., de Jong M., Kooij P.P., Breeman W.A., Bakker W.H., de Herder W.W., van Eijck C.H., Kwekkeboom D.J., Jamar F., Pauwels S. and Valkema R. (1999). Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radio nuclide therapy. Ann Oncol, 10 (Suppl 2), S23–S29.
Kvols L.K., Moertel C.G., O’Connell M.J., Schutt A.J., Rubin J. and Hahn R.G. (1986). Treatment of the malignant carcinoid syndrome: evaluation of a long-acting somatostatin analogue. New Engl J Med, 315, 663–666.
Kwekkeboom D.J., de Herder W.W. and Krenning E.P. (1999). Receptor imaging in the diagnosis and treatment of pituitary tumors. J Endocrinol Invest, 22, 80–88.
Kwekkeboom D., Krenning E.P. and de Jong M. (2000). Peptide receptor imaging and therapy. J Nucl Med, 41, 1704–1713.
Kwekkeboom D.J., Bakker W.H., Kam B.L., Teunissen J.J.M., Kooij P.P.M., Herder W.W., Feelders R.A., Eijck C.H.J., Jong M., Srinivasan A., Erion J.L. and Krenning E.P. (2003). Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTAo,Tyr3] octreotate. Eur J Nucl Med, 30, 417–422.
Lamberts S.W.J., van der Lely A.J., de Herder W.W. and Hofland L.J. (1996). Octreotide. New Engl J Med, 334, 246–254.
Lamberts S.W.J., Hofland L.J. and Nobels F.R. (2001) Neuroendocrine tumor markers. Frontiers Neuroendocrinology, 22, 309–339.
Newman CB, Melmed S, George A, Torigian D, Duhaney M, Snyder P,YoungW, Klibanski A, Molitch ME, Gagel R, Sheeler L, Cook D, Malarkey W,Jackson I, Vance ML,Barkan A, Frohman L and Kleinberg DL. (1998). Octreotide as primary therapy for acromegaly. Journal of Clinical Endocrinology & Metabolism, 83, 3034–3040.
?berg K. (2001). Established clinical use of octreotide and lanreotide in oncology. Chemotherapy, 47 (Suppl 2), 40–53.
Patel Y.C. (1999). Somatostatin and its receptor family. Frontiers Neuroendocrinology, 20, 157–198.
Ren, S., Culler M., Heany T. and Melmed S. (2000). Functional association of sstr2, and sstr5, in suppression of growth hormone secretion. The Endocrine Society Denver, 339 abstract.
Rocheville M., Lange D.C., Kumar U., Sasi R., Patel R.C. and Patel Y.C. (2000a). Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem, 275, 7862–7869.
Rocheville M., Lange D.C., Kumar U., Patel S.C., Patel R.C. and Patel Y.C. (2000b). Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity [see comments). Science, 288, 154–157.
Ruszniewski P., Ducreux M., Chayvialle J.A., Blumberg J., Cloarec D., Michel H., Raymond J.M., Dupas J.L., Gouerou H., Jian R., Genestin E., Bernades P.and Rougier P. (1996). Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients. Gut, 39, 279–283.
Saveanu A., Gunz G., Dufour H., Caron P., Fina F., Ouafik L., Culler M.D., Moreau J.P., Enjalbert A. and Iaquet P. (2001). Bim-23244,a somatostatin receptor subtype 2- and 5selective analog with enhanced efficacy in suppressing growth hormone (GH) from octreotide-resistant human GH-secreting adenomas. Journal of Clinical Endocrinology & Metabolism, 86, 140–145.
Scarpignato C. and Pelosini I. (2001). Somatostatin analogs for cancer treatment and diagnosis: an overview. Chemotherapy, 47 (Suppl z), 1–29.
Sharma, K., Patel Y.C. and Srikat C.B. (1996). Subtype-selective induction of wild-type P53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol, 10, 1688–1696.
Smith M.C., Liu J., Chen T., Schran H., Yeh C.M., Jamar F.,Valkema R., Bakker W., Kvols L., Krenning E. and Pauwels S. (2000). OctreoTher: ongoing early clinical development of a somatostatin-receptor-targeted radionuclide antineoplastic therapy. Digestion, 62 (Suppl 1), 69–72.
Tiensuu Janson E.T., Westlin J.E., Eriksson B., Ahlstrom H., Nilsson S and Oberg K. (1994). [111111In-DTPA-D-Phe1] octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment. Eur J Endocrinol, 131, 577–581.
Trendle M.C., Moertel C.G. and Kvols L.K. (1997). Incidence and morbidity of cholelithiasis in patients receiving chronic octreotide for metastatic carcinoid and malignant islet cell tumors. Cancer, 79, 830–834.
van Eijck, C.H. Krenning E.P., Bootsma A.H., Oei H.Y., van Pel R.. Lindemans J., Jeekel J.J., Reubi J.C and Lamberts S.W. (1994). Somatostatin-receptor scintigraphy in primary breast cancer [see comments]. Lancet, 343, 640–643.
Verhelst J.A., Pedroncelli A.M., Abs R., Montini M., Vandeweghe M.V., Albani G., Maiter D., Pagani M.D., Legros J.J., Gianola D., Bex M., Poppe K., Mockel J. and Pagani G.(2000). Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients. Eur J Endocrinol, 143, 577–584.
Virgolini L, Traub T., Leimer M., Novotny C, Pangerl T., Ofluoglu S., Halvadjieva E., Smith-Jones P., Flores J., Li S.R., Angelberger P., Havlik E., Andreae F., Raderer M., Kurtaran A., Niederle B. and Dudczak R.(2000). New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy. Q Journal of Nuclear Medicine, 44, 50–58.
Warnet A., Harris A.G., Renard E., Martin D., James-Deidier A. and Chaumet-Riffaud P. (1997). A prospective multicenter trial of octreotide in 24 patients with visual defects caused by nonfunctioning and gonadotropin-secreting pituitary adenomas. French Multicenter Octreotide Study Group. Neurosurgery, 41, 786–795.
Wymenga A.N., Eriksson B., Salmela P.I., Jacobsen M.B., Van Cutsem E.J., Fiasse R.H., Valimaki M.J., Renstrup J., de Vries E.G. and Oberg K.E. (1999). Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms. J Clin Oncol, 17, 1111.
Zatelli M.C, Tagliati F., Taylor J.E., Rossi R., Culler M.D. and Uberti E.C (2001). Somatostatin receptor subtypes 2 and 5 differentially affect proliferation in vitro of the human medullary thyroid carcinoma cell line tt. Journal of Clinical Endocrinology & Metabolism, 86, 2161–2169.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer-Verlag Italia
About this paper
Cite this paper
de Herder, W.W., Lamberts, S.W.J. (2003). Somatostatin in Clinical Endocrinology. In: Müller, E.E. (eds) Peptides and Non Peptides of Oncologic and Neuroendocrine Relevance. Springer, Milano. https://doi.org/10.1007/978-88-470-2085-6_8
Download citation
DOI: https://doi.org/10.1007/978-88-470-2085-6_8
Publisher Name: Springer, Milano
Print ISBN: 978-88-470-2170-9
Online ISBN: 978-88-470-2085-6
eBook Packages: Springer Book Archive