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Cortistatin: Not Simply a Natural Somatostatin Analogue

  • Conference paper
Peptides and Non Peptides of Oncologic and Neuroendocrine Relevance

Abstract

Cortistatin (CST) is a recently described peptide mostly expressed in cerebral cortex and hippocampus, but also in peripheral tissues such as fetal heart and lung, prostate, colon and the immune system (de Lecea et al., 1997a, de Lecea et al., 1997b; Fukusumi et al., 1997; Spier and de Lecea, 2000; Dalm et al., 2003). Pre-pro-CST shows high structural homology with pre-pro-somatostatin (pre-pro-SST), particularly in the carboxyl terminus from which SST-14 and SST-28 are enzymatically processed ( Spier and de Lecea, 2000). Interestingly, rat pre-pro-CST may also be cleaved to pro-CST from which the two mature products CST-14 and CST-29 can be generated in rats (de Lecea et al., 1996; Spier and de Lecea, 2000) and CST-17 and CST-29 in humans (de Lecea et al., 1997a; Fukusumi et al., 1997; Spier and de Lecea, 2000). CST-14 shares 11 of the 14 amino acid residues with SST-14, although these peptides are encoded by distinct genes (de Lecea et al., 1996 Spier and de Lecea, 2000).

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References

  • Arosio M., Ronchi C.L., Gebbia C., Cappiello V., Beck-Peccoz P. and Peracchi M. (2003). Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. JClin Endocrinol Metab,88, 701–704.

    Article  CAS  Google Scholar 

  • Bluet-Pajot M.T., Tolle V., Zizzari P., Robert C., Hammond C., Mitchell V., Beauvillain J.C., Viollet C., Epelbaum J. and Kordon C. (2001). Growth hormone secretagogues and hypothalamic networks. Endocrine, 14, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Broglio F., Arvat E., Benso A., Gottero C., Prodam F., Grottoli S., Papotti M., Muccioli G., van der Lely A.J., Deghenghi R. and Ghigo E. (2002a). Endocrine activities of cortis-tatin-14 and its interaction with GHRH and ghrelin in humans. J Clin Endocrinol Metab, 87, 3783–3790.

    Article  Google Scholar 

  • Broglio F., Van Koetsveld P., Benso A., Gottero C, Prodam F., Papotti M., Muccioli G., Gauna C, Hofland L., Deghenghi R., Arvat E., van der Lely AJ. and Ghigo E. (2002b). Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans. J Clin Endocrinol Metab, 87, 4829–4832.

    Article  Google Scholar 

  • Broglio E, Benso A., Gottero C, Prodam E, Gauna C, Filtri L., Arvat E., van der Lely A.J., Deghenghi R. and Ghigo E. (2003). Non-acylated-ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin. J Endocrinol Invest, 26, 192–196.

    PubMed  CAS  Google Scholar 

  • Calbet M., Guadano-Ferraz A., Spier A.D., Maj M., Sutcliffe J.G., Przewlocki R. and de Lecea L. (1999). Cortistatin and somatostatin mRNAs are differentially regulated in response to kainate. Brain Res Mol Brain Res, 72, 55–64.

    Article  PubMed  CAS  Google Scholar 

  • Casanueva F.F. (1992). Physiology of growth hormone secretion and action. In Endocrinology and Metabolism Clinics of North America, ed. Melmed S., pp. 483–517. Philadelphia, Saunders.

    Google Scholar 

  • Cassoni P., Papotti M., Ghe C, Catapano R, Sapino A., Graziani A., Deghenghi R., Reissmann T., Ghigo E. and Muccioli G. (2001). Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab, 86, 1738–1745.

    Article  PubMed  CAS  Google Scholar 

  • Cunha S.R., Mayo K.E. (2002). Ghrelin and growth hormone (GH) secretagogues potentiate GH-releasing hormone (GHRH)-induced cyclic adenosine 3′, 5′-monophosphate production in cells expressing transfected GHRH and GH secretagogue receptors. Endocrinology, 143, 4570–4582.

    Article  PubMed  CAS  Google Scholar 

  • Daim V.A., van Hagen P.M., van Koetsveld P.M., Langerak A.W., van der Lely A.J., Lamberts S.W. and Hofland L.J. (2003). Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system. J Clin Endocrinol Metabol, 88, 270–276.

    Article  Google Scholar 

  • de Lecea L., Criado J.R., Prospero-Garcia O., Gautvik K.M., Schweitzer P., Danielson P.E., Dunlop CL., Siggins G.R., Henriksen S.J. and Sutcliffe J.G. (1996). A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature, 381, 242–245.

    Article  PubMed  CAS  Google Scholar 

  • de Lecea L., Ruiz-Lozano P., Danielson P.E., Peelle-Kirley J., Foye P.E., Frankel W.N. and Sutcliffe J.G. (1997a). Cloning, mRNA expression, and chromosomal mapping of mouse and human preprocortistatin. Genomics, 42, 499–506.

    Article  Google Scholar 

  • de Lecea L., del Rio J.A., Criado J.R., Alcantara S., Morales M., Danielson P.E., Henriksen S.J., Soriano E. and Sutcliffe J.G. (1997b). Cortistatin is expressed in a distinct subset of cortical interneurons. J Neurosci, 17, 5868–5880.

    Google Scholar 

  • Deghenghi R., Papotti M., Ghigo E. and Muccioli G. (2001a). Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland. J Endocrinol Invest, 24, RC1–RC3.

    CAS  Google Scholar 

  • Deghenghi R., Papotti M., Ghigo E., Muccioli G. and Locatelli V. (2001b). Somatostatin octapeptides (lanreotide, octreotide, vapreotide, and their analogs) share the growth hormone-releasing peptide receptor in the human pituitary gland. Endocrine, 14, 29–33.

    Article  Google Scholar 

  • Deghenghi R., Avallone R., Torsello A., Muccioli G., Ghigo E. and Locatelli V. (2001c). Growth hormone-inhibiting activity of cortistatin in the rat. J Endocrinol Invest, 24, RC31–RC33.

    CAS  Google Scholar 

  • Fukusumi S., Kitada C, Takekawa S., Kizawa H., Sakamoto J., Miyamoto M., Hinuma S., Kitano K. and Fujino M. (1997). Identification and characterization of a novel human cortistatin-like peptide. Biochem Biophys Res Commun, 232, 157–163.

    Article  PubMed  CAS  Google Scholar 

  • Ghigo E., Arvat E., Gianotti L., Maccario M. and Camanni F. (1999). The regulation of growth hormone secretion. In The Endocrine Response to Acute Illness, eds. Jenkins R.C. and Ross R.J.M., Frontiers of Hormone Research, pp. 152–175. Basel, Karger.

    Google Scholar 

  • Ghigo E., Arvat E., Giordano R., Broglio E, Gianotti L., Maccario M., Bisi G., Graziani A., Papotti M., Muccioli G., Deghenghi R. and Camanni F. (2001). Biologic activities of growth hormone secretagogues in humans. Endocrine, 14, 87–93.

    Article  PubMed  CAS  Google Scholar 

  • Gnanapavan S., Kola B., Bustin S.A., Morris D.G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A.B. and Korbonits M. (2002). The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab, 87, 2988–2991.

    Article  PubMed  CAS  Google Scholar 

  • Goth M.I., Lyons C.E., Canny B.J. and Thorner M.O. (1992). Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing peptide and GH-releasing hormone stimulate GH release through distinct pituitary receptors. Endocrinology, 130, 939–944.

    Article  PubMed  CAS  Google Scholar 

  • Hosoda H., Kojima M., Matsuo H. and Kangawa K. (2000). Purification and characterization of rat des-Glni4-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem, 275, 1995–2000.

    Article  Google Scholar 

  • Kamegai J., Tamura H., Shimizu T., Ishii S., Sugihara H. and Wakabayashi I. (2000). Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression. Endocrinology, 141, 4797–4800.

    Article  PubMed  CAS  Google Scholar 

  • Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H. and Kangawa K. (1999)- Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402, 656–660.

    Article  PubMed  CAS  Google Scholar 

  • Kojima M., Hosoda H., Matsuo H. and Kangawa K. (2001a). Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab, 12, 118–122.

    Article  Google Scholar 

  • Kojima M., Hosoda H. and Kangawa K. (2001b). Purification and distribution of ghrelin: the natural endogenous ligand for the growth hormone secretagogue receptor. Hormone Res, 56, 93–97.

    Article  Google Scholar 

  • Kreienkamp H.J. (1999). Molecular biology of the receptors for somatostatin and cortistatin. Results Probl Cell Differ, 26, 215–237.

    PubMed  CAS  Google Scholar 

  • Maheshwari H.G., Rahim A., Shalet S.M. and Baumann G. (1999). Selective lack of growth hormone (GH) response to the GH-releasing peptide hexarelin in patients with GH-releasing hormone receptor deficiency. J Clin Endocrinol Metab, 84, 956–959.

    Article  PubMed  CAS  Google Scholar 

  • Massoud A.F., Hindmarsh P.C. and Brook CG. (1997). Interaction of the growth hormone releasing peptide hexarelin with somatostatin. Clin Endocrinol, 47, 537–547.

    Article  CAS  Google Scholar 

  • Muccioli G., Ghe C, Ghigo M.C., Papotti M., Arvat E., Boghen M.F., Nilsson M.H., Deghenghi R., Ong H. and Ghigo E. (1998). Specific receptors for synthetic GH secretagogues in the human brain and pituitary gland. J Endocrinol, 157, 99–106.

    Article  PubMed  CAS  Google Scholar 

  • Muccioli G., Broglio F., Valetto M.R., Ghe C, Catapano R, Graziani A., Papotti M., Bisi G., Deghenghi R. and Ghigo E. (2000). Growth hormone-releasing peptides and the cardiovascular system. Ann Endocrinol, 61, 27–31.

    CAS  Google Scholar 

  • Muccioli G., Papotti M., Locatelli V., Ghigo E. and Deghenghi R. (2001). Binding of 125Ilabeled ghrelin to membranes from human hypothalamus and pituitary gland. J Endocrinol Invest, 24, RC7–RC9.

    PubMed  CAS  Google Scholar 

  • Muccioli G., Tschop M., Papotti M., Deghenghi R., Heiman M. and Ghigo E. (2002a). Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity. Eur J Pharmacol, 440, 235–254.

    Article  Google Scholar 

  • Muccioli G. (2002b). Interplay between ghrelin, somatostatin and cortistatin. In Hormones. Body Composition and Physical Performances, pp. 51 (abstract). Turin, Italy, 15-17 November 2002.

    Google Scholar 

  • Ong H., Bodart V., McNicoll N., Lamontagne D. and Bouchard J.F. (1998). Binding sites for growth hormone-releasing peptide. Growth Horm IGF Res, 8, 137–140.

    Article  PubMed  CAS  Google Scholar 

  • Pandya N., DeMott-Friberg R., Bowers C.Y., Barkan A.L. and Jaffe C.A. (1998). Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH-releasing hormone for maximal GH stimulation. J Clin Endocrinol Metab, 83, 1186–1189.

    Article  PubMed  CAS  Google Scholar 

  • Papotti M., Ghe C., Cassoni P., Catapano R, Deghenghi R., Ghigo E. and Muccioli G. (2000). Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab, 85, 3803–3807.

    Article  PubMed  CAS  Google Scholar 

  • Popovic V., Damjanovic S., Mick D., Djurovic M., Dieguez C. and Casanueva F.F. (1995). Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. J Clin Endocrinol Metab, 80, 942–947.

    Article  PubMed  CAS  Google Scholar 

  • Reichlin S. (1998). Neuroendocrinology. In: Williams Textbook of Endocrinology, 9th edn, ed. Wilson J.D., pp. 165–248. Philadelphia, Saunders.

    Google Scholar 

  • Sanchez-Alavez M., Gomez-Chavarin M., Navarro L., Jimenez-Anguiano A., Murillo-Rodriguez E., Prado-Alcala R.A., Drucker-Colin R. and Prospero-Garcia O. (2000). Cortistatin modulates memory processes in rats. Brain Res, 858, 78–83.

    Article  PubMed  CAS  Google Scholar 

  • Siehler S., Seuwen K. and Hoyer D. (1998). [i25lJTyrio-cortistatini4 labels all five somatostatin receptors. Naunyn Schmiedebergs Arch Pharmacol, 357, 483–489.

    Article  PubMed  CAS  Google Scholar 

  • Smith R.G., Van der Ploeg L.H., Howard A.D., Feighner S.D., Cheng K., Hickey G.J., Wyvratt MJ. Jr., Fisher M.H., Nargund R.P. and Patchett A.A. (1997). Peptidomimetic regulation of growth hormone secretion. Endocrine Rev, 18, 621-645.

    Article  CAS  Google Scholar 

  • Smith R.G., Griffin RR., Xu Y., Smith A.G., Liu K., Calacay J., Feighner S.D., Pong C, Leong D., Pomes A., Cheng K., Van der Ploeg L.H., Howard A.D., Schaeffer J. and Leonard R.J. (2000). Adenosine: a partial agonist of the growth hormone secretagogue receptor. Biochem Biophys Res Commun, 276, 1306–1313.

    Article  PubMed  CAS  Google Scholar 

  • Spier A.D. and de Lecea L. (2000). Cortistatin: a member of the somatostatin neuropeptide family with distinct physiological functions. Brain Res Brain Res Rev, 33, 228–241.

    Article  PubMed  CAS  Google Scholar 

  • Tannenbaum G.S. and Bowers C.Y. (2001). Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin. Endocrine, 14, 21–27.

    Article  PubMed  CAS  Google Scholar 

  • Tullin S., Hansen B.S., Ankersen M., Moller J., Von Cappelen K.A. and Thim L. (2000). Adenosine is an agonist of the growth hormone secretagogue receptor. Endocrinology, 141, 3397–3402.

    Article  PubMed  CAS  Google Scholar 

  • Vasilaki A., Lanneau C, Dournaud P., de Lecea L., Gardette R. and Epelbaum J. (1999). Cortistatin affects glutamate sensitivity in mouse hypothalamic neurons through activation of sst2 somatostatin receptor subtype. Neuroscience, 88, 359–364.

    Article  PubMed  CAS  Google Scholar 

  • Wren A.M., Small C.J., Fribbens C.V., Neary N.M., Ward H.L., Seal L.J., Ghatei M.A. and Bloom S.R. (2002). The hypothalamic mechanisms of the hypophysiotropic action of ghrelin. Neuroendocrinology, 76, 316–324.

    Article  PubMed  CAS  Google Scholar 

  • Yoshihara E, Kojima M., Hosoda H., Nakazato M. and Kangawa K. (2002). Ghrelin: a novel peptide for growth hormone release and feeding regulation. Curr Opin Clin Nutr Metab Care, 5, 391–395.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. R. Deghenghi
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  2. F. Broglio
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  3. F. Prodam
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  4. C. Gottero
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  5. M. Papotti
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  6. G. Muccioli
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  7. E. Ghigo
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Editors and Affiliations

  1. Department of Pharmacology, University of Milan, Milan, Italy

    Eugenio E. Müller

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© 2003 Springer-Verlag Italia

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Deghenghi, R. et al. (2003). Cortistatin: Not Simply a Natural Somatostatin Analogue. 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_6

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  • DOI: https://doi.org/10.1007/978-88-470-2085-6_6

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-2170-9

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