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SST  -  somatostatin

Homo sapiens

Synonyms: Growth hormone release-inhibiting factor, SMST, Somatostatin
 
 
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Disease relevance of SST

 

Psychiatry related information on SST

 

High impact information on SST

 

Chemical compound and disease context of SST

 

Biological context of SST

  • Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion [20].
  • Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM) [20].
  • The catalytically inactive mutant of SHP-1 (SHP-1C455S) abolished the ability of the SST agonists to signal apoptosis by preventing the recruitment of wild type SHP-1 to the membrane [21].
  • Here we have investigated the molecular basis of hSSTR1 up-regulation. hSSTR1 was up-regulated by SST in a time-, temperature-, and dose-dependent manner to saturable levels, in intact cells but not in membrane preparations [22].
  • High affinity binding sites for SST and mRNA for SST-2 receptor subtype were detected in U-87 MG tumors [2].
 

Anatomical context of SST

 

Associations of SST with chemical compounds

  • Cross-competition between VIP and SST/OCT for binding to tumor cells was observed [20].
  • Experiments also included groups that were administered RC-121 prior to the injection of AN-238, and groups injected with AN-162, a cytotoxic SST analogue similar to AN-238 but containing DOX instead of AN-201 [2].
  • MIN6 cells over-expressing PIST display enhanced glucose-stimulated insulin secretion and a decreased sensitivity to SST-induced inhibition of insulin secretion [27].
  • The most commonly applied SST analogues are octreotide (OCT) and lanreotide (LAN), which are both available in a slow release formulation [28].
  • RESULTS: Our search disclosed 22 case reports, five phase 1 and 47 phase II trials, and eight randomised clinical trials using SST analogues (octreotide, lanreotide and vapreotide) as antineoplastic agents [29].
 

Physical interactions of SST

 

Enzymatic interactions of SST

  • SHP-1 was phosphorylated on tyrosine in control cells and somatostatin induced a rapid and transient dephosphorylation on tyrosine residues of the enzyme [34].
  • However, Tax did not form a complex on the somatostatin CRE in the presence of either phosphorylated or non-phosphorylated CREB and it did not stimulate CBP association to this element [35].
 

Co-localisations of SST

 

Regulatory relationships of SST

 

Other interactions of SST

 

Analytical, diagnostic and therapeutic context of SST

  • In spite of successful blocking of tumoral SST receptors as judged by SST receptor scintigraphy and subjective improvement of symptoms, the patient had progressive disease [28].
  • Carefully designed clinical trials including investigation of SSTR status before treatment, evaluation of an indirect mechanism of SST analogues, and assessment of optimal combination of hormone therapy and chemotherapy with SST analogues are clearly needed in the near future [29].
  • Apart from these indications, the data do not justify recommendation of SST analogues as antineoplastic agents outside of clinical trials, as the optimal dose and schedule of application for antineoplastic activity has not been defined for currently used agents [29].
  • High affinity binding sites for SST are present in H-69 SCLC and were now detected in H-157 non-SCLC xenografts, but not in H-157 cells [48].
  • SST or SST-like immunoreactivity was detected by radioimmunoassay in tissue extract from ciliary processes and in aqueous humor [49].

References

  1. High expression of somatostatin receptors and messenger ribonucleic acid for its receptor subtypes in organ-confined and locally advanced human prostate cancers. Halmos, G., Schally, A.V., Sun, B., Davis, R., Bostwick, D.G., Plonowski, A. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  2. Regression of U-87 MG human glioblastomas in nude mice after treatment with a cytotoxic somatostatin analog AN-238. Kiaris, H., Schally, A.V., Nagy, A., Sun, B., Szepeshazi, K., Halmos, G. Clin. Cancer Res. (2000) [Pubmed]
  3. Polymorphisms in genes involved in GH1 release and their association with breast cancer risk. Wagner, K., Hemminki, K., Grzybowska, E., Klaes, R., Burwinkel, B., Bugert, P., Schmutzler, R.K., Wappenschmidt, B., Butkiewicz, D., Pamula, J., Pekala, W., Försti, A. Carcinogenesis (2006) [Pubmed]
  4. Octapeptide somatostatin analog SMS 201-995 induces translocation of intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells. Srikant, C.B., Shen, S.H. Endocrinology (1996) [Pubmed]
  5. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Garbrecht, N., Anlauf, M., Schmitt, A., Henopp, T., Sipos, B., Raffel, A., Eisenberger, C.F., Knoefel, W.T., Pavel, M., Fottner, C., Musholt, T.J., Rinke, A., Arnold, R., Berndt, U., Plöckinger, U., Wiedenmann, B., Moch, H., Heitz, P.U., Komminoth, P., Perren, A., Klöppel, G. Endocr. Relat. Cancer (2008) [Pubmed]
  6. Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus. Goodyer, C.G., Grigorakis, S.I., Patel, Y.C., Kumar, U. Neuroscience (2004) [Pubmed]
  7. Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease. Beal, M.F., Mazurek, M.F., Tran, V.T., Chattha, G., Bird, E.D., Martin, J.B. Science (1985) [Pubmed]
  8. Effect of somatostatin infusion on the somatotrope responsiveness to growth hormone-releasing hormone in patients with anorexia nervosa. Gianotti, L., Rolla, M., Arvat, E., Belliti, D., Valetto, M.R., Ferdeghini, M., Ghigo, E., Müller, E.E. Biol. Psychiatry (1999) [Pubmed]
  9. Somatostatin analogs in oncology: a look to the future. Jenkins, S.A., Kynaston, H.G., Davies, N.D., Baxter, J.N., Nott, D.M. Chemotherapy. (2001) [Pubmed]
  10. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Rocheville, M., Lange, D.C., Kumar, U., Patel, S.C., Patel, R.C., Patel, Y.C. Science (2000) [Pubmed]
  11. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. Calès, P., Masliah, C., Bernard, B., Garnier, P.P., Silvain, C., Szostak-Talbodec, N., Bronowicki, J.P., Ribard, D., Botta-Fridlund, D., Hillon, P., Besseghir, K., Lebrec, D. N. Engl. J. Med. (2001) [Pubmed]
  12. Treatment of type II gastric carcinoid tumors with somatostatin analogues. Tomassetti, P., Migliori, M., Caletti, G.C., Fusaroli, P., Corinaldesi, R., Gullo, L. N. Engl. J. Med. (2000) [Pubmed]
  13. Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors. Virgolini, I., Raderer, M., Kurtaran, A., Angelberger, P., Banyai, S., Yang, Q., Li, S., Banyai, M., Pidlich, J., Niederle, B., Scheithauer, W., Valent, P. N. Engl. J. Med. (1994) [Pubmed]
  14. Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. Gutniak, M., Orskov, C., Holst, J.J., Ahrén, B., Efendic, S. N. Engl. J. Med. (1992) [Pubmed]
  15. Preserved insulin secretion and insulin independence in recipients of islet autografts. Pyzdrowski, K.L., Kendall, D.M., Halter, J.B., Nakhleh, R.E., Sutherland, D.E., Robertson, R.P. N. Engl. J. Med. (1992) [Pubmed]
  16. The phosphotyrosine phosphatase eta mediates somatostatin inhibition of glioma proliferation via the dephosphorylation of ERK1/2. Massa, A., Barbieri, F., Aiello, C., Iuliano, R., Arena, S., Pattarozzi, A., Corsaro, A., Villa, V., Fusco, A., Zona, G., Spaziante, R., Schettini, G., Florio, T. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  17. Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes. Vinik, A.I., Tsai, S.T., Moattari, A.R., Cheung, P., Eckhauser, F.E., Cho, K. Am. J. Med. (1986) [Pubmed]
  18. Somatostatin receptor genes are expressed in lymphocytes from retroorbital tissues in Graves' disease. Pasquali, D., Notaro, A., Bonavolonta', G., Vassallo, P., Bellastella, A., Sinisi, A.A. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  19. Expression of somatostatin receptor subtypes in cultured astrocytes and gliomas. Feindt, J., Becker, I., Blömer, U., Hugo, H.H., Mehdorn, H.M., Krisch, B., Mentlein, R. J. Neurochem. (1995) [Pubmed]
  20. Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors. Virgolini, I., Yang, Q., Li, S., Angelberger, P., Neuhold, N., Niederle, B., Scheithauer, W., Valent, P. Cancer Res. (1994) [Pubmed]
  21. Regulation of acidification and apoptosis by SHP-1 and Bcl-2. Thangaraju, M., Sharma, K., Leber, B., Andrews, D.W., Shen, S.H., Srikant, C.B. J. Biol. Chem. (1999) [Pubmed]
  22. Agonist-dependent up-regulation of human somatostatin receptor type 1 requires molecular signals in the cytoplasmic C-tail. Hukovic, N., Rocheville, M., Kumar, U., Sasi, R., Khare, S., Patel, Y.C. J. Biol. Chem. (1999) [Pubmed]
  23. Somatostatin and its receptor family. Patel, Y.C. Frontiers in neuroendocrinology. (1999) [Pubmed]
  24. Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors. Carlton, S.M., Du, J., Davidson, E., Zhou, S., Coggeshall, R.E. Pain (2001) [Pubmed]
  25. Inhibitory effect of pasireotide and octreotide on lymphocyte activation. Lattuada, D., Casnici, C., Crotta, K., Mastrotto, C., Franco, P., Schmid, H.A., Marelli, O. J. Neuroimmunol. (2007) [Pubmed]
  26. Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy. Pasquali, D., Vassallo, P., Esposito, D., Bonavolontà, G., Bellastella, A., Sinisi, A.A. J. Mol. Endocrinol. (2000) [Pubmed]
  27. The PDZ/coiled-coil domain containing protein PIST modulates insulin secretion in MIN6 insulinoma cells by interacting with somatostatin receptor subtype 5. Wente, W., Efanov, A.M., Treinies, I., Zitzer, H., Gromada, J., Richter, D., Kreienkamp, H.J. FEBS Lett. (2005) [Pubmed]
  28. Different response to the long-acting somatostatin analogues lanreotide and octreotide in a patient with a malignant carcinoid. Raderer, M., Kurtaran, A., Scheithauer, W., Fiebiger, W., Weinlaender, G., Oberhuber, G. Oncology (2001) [Pubmed]
  29. The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing? Hejna, M., Schmidinger, M., Raderer, M. Ann. Oncol. (2002) [Pubmed]
  30. 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. Shimon, I., Yan, X., Taylor, J.E., Weiss, M.H., Culler, M.D., Melmed, S. J. Clin. Invest. (1997) [Pubmed]
  31. Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Yamada, Y., Reisine, T., Law, S.F., Ihara, Y., Kubota, A., Kagimoto, S., Seino, M., Seino, Y., Bell, G.I., Seino, S. Mol. Endocrinol. (1992) [Pubmed]
  32. Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2. Ferrante, E., Pellegrini, C., Bondioni, S., Peverelli, E., Locatelli, M., Gelmini, P., Luciani, P., Peri, A., Mantovani, G., Bosari, S., Beck-Peccoz, P., Spada, A., Lania, A. Endocr. Relat. Cancer (2006) [Pubmed]
  33. Cloning and characterization of a fourth human somatostatin receptor. Rohrer, L., Raulf, F., Bruns, C., Buettner, R., Hofstaedter, F., Schüle, R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  34. The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling. Lopez, F., Estève, J.P., Buscail, L., Delesque, N., Saint-Laurent, N., Théveniau, M., Nahmias, C., Vaysse, N., Susini, C. J. Biol. Chem. (1997) [Pubmed]
  35. HTLV-1 21 bp repeat sequences facilitate stable association between Tax and CREB to increase CREB binding affinity. Yin, M.J., Gaynor, R.B. J. Mol. Biol. (1996) [Pubmed]
  36. Colocalization of neuropeptides with calbindin D28k and NADPH diaphorase in the enteric nerve plexuses of normal human ileum. Dhatt, N., Buchan, A.M. Gastroenterology (1994) [Pubmed]
  37. Presence and localization of CCK receptor subtypes in calf pancreas. Morisset, J., Lainé, J., Bourassa, J., Lessard, M., Rome, V., Guilloteau, P. Regul. Pept. (2003) [Pubmed]
  38. Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease. Beal, M.F., Mazurek, M.F., Chattha, G.K., Svendsen, C.N., Bird, E.D., Martin, J.B. Ann. Neurol. (1986) [Pubmed]
  39. Beta-arrestin is involved in the desensitization but not in the internalization of the somatostatin receptor 2A expressed in CHO cells. Brasselet, S., Guillen, S., Vincent, J.P., Mazella, J. FEBS Lett. (2002) [Pubmed]
  40. Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5. Cordelier, P., Estève, J.P., Bousquet, C., Delesque, N., O'Carroll, A.M., Schally, A.V., Vaysse, N., Susini, C., Buscail, L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  41. Characterization of the somatostatin receptor subtype in a bronchial carcinoid tumor responsible for Cushing's syndrome. Lefebvre, H., Jégou, S., Leroux, P., Dero, M., Vaudry, H., Kuhn, J.M. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  42. Ghrelin potentiates growth hormone secretion driven by putative somatostatin withdrawal and resists inhibition by human corticotropin-releasing hormone. Veldhuis, J.D., Iranmanesh, A., Mielke, K., Miles, J.M., Carpenter, P.C., Bowers, C.Y. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  43. Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. Broglio, F., Koetsveld Pv, P., Benso, A., Gottero, C., Prodam, F., Papotti, M., Muccioli, G., Gauna, C., Hofland, L., Deghenghi, R., Arvat, E., Van Der Lely, A.J., Ghigo, E. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  44. Octreotide and related somatostatin analogs in the diagnosis and treatment of pituitary disease and somatostatin receptor scintigraphy. Lamberts, S.W., Hofland, L.J., de Herder, W.W., Kwekkeboom, D.J., Reubi, J.C., Krenning, E.P. Frontiers in neuroendocrinology. (1993) [Pubmed]
  45. NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Gorden, P., Comi, R.J., Maton, P.N., Go, V.L. Ann. Intern. Med. (1989) [Pubmed]
  46. Localization of receptors for vasoactive intestinal peptide, somatostatin, and substance P in distinct compartments of human lymphoid organs. Reubi, J.C., Horisberger, U., Kappeler, A., Laissue, J.A. Blood (1998) [Pubmed]
  47. Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. Mathern, G.W., Babb, T.L., Pretorius, J.K., Leite, J.P. J. Neurosci. (1995) [Pubmed]
  48. A targeted cytotoxic somatostatin (SST) analogue, AN-238, inhibits the growth of H-69 small-cell lung carcinoma (SCLC) and H-157 non-SCLC in nude mice. Kiaris, H., Schally, A.V., Nagy, A., Szepeshazi, K., Hebert, F., Halmos, G. Eur. J. Cancer (2001) [Pubmed]
  49. Somatostatin modulates PI3K-Akt, eNOS and NHE activity in the ciliary epithelium. Ghosh, S., Choritz, L., Geibel, J., Coca-Prados, M. Mol. Cell. Endocrinol. (2006) [Pubmed]
 
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