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Gene Review

CORT  -  cortistatin

Homo sapiens

Synonyms: CST-14, CST-17, CST-29, Cortistatin, MGC32686, ...
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Disease relevance of CORT


Psychiatry related information on CORT

  • METHODS: Prolactin (PRL) and cortisol (CORT) responses to the serotonergic agonist d-fenfluramine (D-fen), clinical psychobehavioral changes, and psychometric measures were evaluated 3 weeks and then 12 months after MDMA discontinuation [6].
  • Prolactin (PRL) and Cortisol (CORT) responses to d,l-fenfluramine (FEN) challenge (60 mg) were examined in patients with affective disorders on two occasions under euthymic conditions: drug-free before admission to prophylactic treatment and after about 9 months of medication with lithium or carbamazepine [7].
  • 3. Evidence for a role of central 5-HT in parasuicide arises from reduced concentrations of lumbar CSF 5-HIAA, reduced PRL responses to d,l-fenfluramine challenge, and increased CORT responses to 5-HTP challenge [8].
  • PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects [9].
  • Mechanisms related to the differences in the interaction of natural (e.g. CORT) and synthetic (e.g. PRED) corticosteroids with the central glucocorticoid and mineralocorticoid receptors may explain the different effects upon psychopathology [10].

High impact information on CORT

  • Cortistatin is a recently discovered cyclic neuropeptide related to somatostatin that has emerged as a potential endogenous antiinflammatory factor based on its production by and binding to immune cells [11].
  • Cortistatin represents a potential multistep therapeutic agent for human septic shock, to be used in combination with other immunomodulatory agents or as a complement to other therapies [11].
  • Cortistatin down-regulated the production of inflammatory mediators by endotoxin-activated macrophages [11].
  • Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia [11].
  • The administration of cortistatin protected against lethality after cecal ligation and puncture, or injection of bacterial endotoxin or Escherichia coli, and prevented the septic shock-associated histopathology, such as infiltration of inflammatory cells and intravascular disseminated coagulation in various target organs [11].

Chemical compound and disease context of CORT


Biological context of CORT


Anatomical context of CORT


Associations of CORT with chemical compounds

  • Neither SRIF nor CST modified glucose levels [20].
  • While the binding of 125I-Tyr-Ala-hexarelin to pituitary membranes was completely displaced by unlabelled hexarelin, ghrelin and CST, none of the SRIH fragments tested inhibited this binding [21].
  • Baseline prolactin (PRL) and cortisol (CORT) and hormonal responses to d-FEN and placebo were measured at hourly intervals over a 4-hour period [4].
  • In contrast, CORT responses in MDMA users were restored after 12 months of abstinence, with significantly higher responses to D-fen, in comparison with 3-week responses (p < .05) [6].
  • CORT restored responses to D-fen at 12 months, and the correlation of neuroendocrine changes with MDMA exposure suggest that the neuroendocrine impairment may be due to a partially reversible neurotoxic action of MDMA on the human brain [6].

Physical interactions of CORT

  • CST binds all 5 SRIF receptors, as well the GH secretagogue (GHS)/ghrelin receptors [19].
  • CONTEXT: Cortistatin binds all somatostatin receptor subtypes but also has particular central actions; moreover, a specific cortistatin receptor has also been discovered [22].
  • Given these findings, the ability of CST to bind the GHS-R1a is of particular relevance because somatostatin and its fragments do not bind the same receptor [23].

Regulatory relationships of CORT

  • CST-14 or CST-17 (10 nm) inhibited basal GH secretion in six of the 13 GH-cell adenomas and two of the three GH-PRL mixed adenomas [2].
  • Both SRIF and CST similarly inhibited (p < 0.01) circulating ghrelin levels of about 55% [20].
  • The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14 [24].
  • We investigated the influence of CORT on pyridostigmine-induced GH responses by testing subjects at 9.00 and 14.00 h [25].
  • The results indicate that a glucocorticoid hormone (CORT) enhances INS induced stimulation of TO activity, as evidenced by enhanced enzyme activity [26].

Other interactions of CORT

  • Cortistatin (CST)-14, a neuropeptide with high homology with somatostatin (SS)-14, binds all sst subtypes but, unlike SS, also ghrelin's receptor [24].
  • The GH-releasing activity of ghrelin seems partially resistant to CST-14 as well as SS-14 [24].
  • Our data demonstrate for the first time that cortistatin, a natural peptide related to SRIH, binds to GHS-R and suggest that this factor may play a role in modulating the activity of these receptors [21].
  • Both SRIF and CST similarly inhibited (p < 0.01) glucagon levels of about 40% [20].
  • It bound to all human somatostatin receptor (SSTR) subtypes in almost the same manner as rat CST-14 [16].

Analytical, diagnostic and therapeutic context of CORT


  1. Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary tumors. Ejeskär, K., Abel, F., Sjöberg, R., Bäckström, J., Kogner, P., Martinsson, T. Cytogenet. Cell Genet. (2000) [Pubmed]
  2. Cortistatin inhibits growth hormone release from human fetal and adenoma pituitary cells and prolactin secretion from cultured prolactinomas. Rubinfeld, H., Hadani, M., Barkai, G., Taylor, J.E., Culler, M.D., Shimon, I. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  3. Ghrelin and cortistatin in lung cancer: Expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line. Cassoni, P., Allia, E., Marrocco, T., Gh??, C., Ghigo, E., Muccioli, G., Papotti, M. J. Endocrinol. Invest. (2006) [Pubmed]
  4. Diminished serotonin-mediated prolactin responses in nondepressed stroke patients compared with healthy normal subjects. Ramasubbu, R., Flint, A., Brown, G., Awad, G., Kennedy, S. Stroke (1998) [Pubmed]
  5. Modification of the responses of endothelin-1 to exhaustive physical exercise under simulated high-altitude conditions with acute hypoxia. Kullmer, T., Jungmann, E., Haak, T., Usadel, K.H. Metab. Clin. Exp. (1995) [Pubmed]
  6. Long-lasting effects of (+/-)3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans. Gerra, G., Zaimovic, A., Ferri, M., Zambelli, U., Timpano, M., Neri, E., Marzocchi, G.F., Delsignore, R., Brambilla, F. Biol. Psychiatry (2000) [Pubmed]
  7. 5-HT brain function in affective disorder: d,l-fenfluramine-induced hormone release and clinical outcome in long-term lithium/carbamazepine prophylaxis. Mannel, M., Müller-Oerlinghausen, B., Czernik, A., Sauer, H. Journal of affective disorders. (1997) [Pubmed]
  8. Central serotonergic function in parasuicide. Coccaro, E.F., Astill, J.L. Prog. Neuropsychopharmacol. Biol. Psychiatry (1990) [Pubmed]
  9. Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates. Gerra, G., Zaimovic, A., Raggi, M.A., Giusti, F., Delsignore, R., Bertacca, S., Brambilla, F. Drug and alcohol dependence. (2001) [Pubmed]
  10. Differential mood response to natural and synthetic corticosteroids after bilateral adrenalectomy: a case report. Seifritz, E., Hemmeter, U., Pöldinger, W., Froesch, E.R., Reul, J.M., Holsboer-Trachsler, E. Journal of psychiatric research. (1994) [Pubmed]
  11. Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia. Gonzalez-Rey, E., Chorny, A., Robledo, G., Delgado, M. J. Exp. Med. (2006) [Pubmed]
  12. Neuroendocrine and behavioural responses to opioid receptor-antagonist during heroin detoxification: relationship with personality traits. Gerra, G., Ceresini, S., Esposito, A., Zaimovic, A., Moi, G., Bussandri, M., Raggi, M.A., Molina, E. International clinical psychopharmacology. (2003) [Pubmed]
  13. Cortistatin: a member of the somatostatin neuropeptide family with distinct physiological functions. Spier, A.D., de Lecea, L. Brain Res. Brain Res. Rev. (2000) [Pubmed]
  14. Structural and compositional determinants of cortistatin activity. Criado, J.R., Li, H., Jiang, X., Spina, M., Huitrón-Reséndiz, S., Liapakis, G., Calbet, M., Siehler, S., Henriksen, S.J., Koob, G., Hoyer, D., Sutcliffe, J.G., Goodman, M., de Lecea, L. J. Neurosci. Res. (1999) [Pubmed]
  15. Method for efficient transfection of in vitro-transcribed mRNA into SK-N-AS and HEK293 cells: difference in the toxicity of nuclear EGFP compared to cytoplasmic EGFP. Ejeskär, K., Fransson, S., Zaibak, F., Ioannou, P.A. Int. J. Mol. Med. (2006) [Pubmed]
  16. Identification and characterization of a novel human cortistatin-like peptide. Fukusumi, S., Kitada, C., Takekawa, S., Kizawa, H., Sakamoto, J., Miyamoto, M., Hinuma, S., Kitano, K., Fujino, M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  17. A subset of kappa opioid ligands bind to the membrane glucocorticoid receptor in an amphibian brain. Evans, S.J., Searcy, B.T., Moore, F.L. Endocrinology (2000) [Pubmed]
  18. Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system. Dalm, V.A., van Hagen, P.M., van Koetsveld, P.M., Langerak, A.W., van der Lely, A.J., Lamberts, S.W., Hofland, L.J. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  19. Presence of cortistatin in the human pancreas. Papotti, M., Tarabra, E., Allia, E., Bozzalla-Cassione, F., Broglio, F., Deghenghi, R., Ghigo, E., Muccioli, G. J. Endocrinol. Invest. (2003) [Pubmed]
  20. 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]
  21. Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland. Deghenghi, R., Papotti, M., Ghigo, E., Muccioli, G. J. Endocrinol. Invest. (2001) [Pubmed]
  22. Cortistatin-17 and somatostatin-14 display the same effects on growth hormone, prolactin, and insulin secretion in patients with acromegaly or prolactinoma. Grottoli, S., Gasco, V., Broglio, F., Baldelli, R., Ragazzoni, F., Gallenca, F., Mainolfi, A., Prodam, F., Muccioli, G., Ghigo, E. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  23. Somatostatin, cortistatin, ghrelin and glucose metabolism. Gauna, C., van der Lely, A.J. J. Endocrinol. Invest. (2005) [Pubmed]
  24. Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans. Broglio, F., Arvat, E., Benso, A., Gottero, C., Prodam, F., Grottoli, S., Papotti, M., Muccioli, G., van der Lely, A.J., Deghenghi, R., Ghigo, E. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  25. Time dependency of pyridostigmine-induced growth hormone response. Thakore, J.H., Coffey, I., Dinan, T.G. Journal of basic and clinical physiology and pharmacology. (1994) [Pubmed]
  26. Insulin modulates rat liver glucocorticoid receptor. Isenovic, E.R., Zakula, Z., Koricanac, G., Ribarac-Stepic, N. Acta. Biol. Hung. (2006) [Pubmed]
  27. Direct effect of cortistatin on GH release from cultured pituitary cells in the rat. Baranowska, B., Chmielowska, M., Wolinska-Witort, E., Bik, W., Baranowska-Bik, A., Martynska, L. Neuro Endocrinol. Lett. (2006) [Pubmed]
  28. Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents. Stoff, D.M., Pasatiempo, A.P., Yeung, J., Cooper, T.B., Bridger, W.H., Rabinovich, H. Psychiatry research. (1992) [Pubmed]
  29. Endocrine responses after d-fenfluramine and ipsapirone challenge: further support for Cloninger's tridimensional model of personality. Hennig, J., Toll, C., Schonlau, P., Rohrmann, S., Netter, P. Neuropsychobiology (2000) [Pubmed]
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