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Cortistatin-8, a synthetic cortistatin-derived ghrelin receptor ligand, does not modify the endocrine responses to acylated ghrelin or hexarelin in humans.
Neuropeptides. 2008 Feb; 42(1):89-93.N

Abstract

Cortistatin (CST), a neuropeptide with high structural homology with somatostatin (SST), binds all SST receptor (SST-R) subtypes but, unlike SST, also shows high binding affinity to ghrelin receptor (GHS-R1a). CST exerts the same endocrine activities of SST in humans, suggesting that the activation of the SST-R might mask the potential interaction with ghrelin system. CST-8, a synthetic CST-analogue devoid of any binding affinity to SST-R but capable to bind the GHS-R1a, has been reported able to exert antagonistic effects on ghrelin actions either in vitro or in vivo in animals. We studied the effects of CST-8 (2.0 microg/kg i.v. as a bolus or 2.0 microg/kg/h i.v. as infusion) on both spontaneous and ghrelin- or hexarelin- (1.0 microg/kg i.v. as bolus) stimulated GH, PRL, ACTH and cortisol secretion in 6 normal volunteers. During saline, no change occurred in GH and PRL levels while a spontaneous ACTH and cortisol decrease was observed. As expected, both ghrelin and hexarelin stimulated GH, PRL, ACTH and cortisol secretion (p<0.05). CST-8, administered either as bolus or as continuous infusion, did not modify both spontaneous and ghrelin- or hexarelin-stimulated GH, PRL, ACTH and cortisol secretion. In conclusion, CST-8 seems devoid of any modulatory action on either spontaneous or ghrelin-stimulated somatotroph, lactotroph and corticotroph secretion in humans in vivo. These negative results do not per se exclude that, even at these doses, CST-8 might have some neuroendocrine effects after prolonged treatment or that, at higher doses, may be able to effectively antagonize ghrelin action in humans. However, these data strongly suggest that CST-8 is not a promising candidate as GHS-R1a antagonist for human studies to explore the functional interaction between ghrelin and cortistatin systems.

Authors+Show Affiliations

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Turin, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18061663

Citation

Prodam, F, et al. "Cortistatin-8, a Synthetic Cortistatin-derived Ghrelin Receptor Ligand, Does Not Modify the Endocrine Responses to Acylated Ghrelin or Hexarelin in Humans." Neuropeptides, vol. 42, no. 1, 2008, pp. 89-93.
Prodam F, Benso A, Gramaglia E, et al. Cortistatin-8, a synthetic cortistatin-derived ghrelin receptor ligand, does not modify the endocrine responses to acylated ghrelin or hexarelin in humans. Neuropeptides. 2008;42(1):89-93.
Prodam, F., Benso, A., Gramaglia, E., Lucatello, B., Riganti, F., van der Lely, A. J., Deghenghi, R., Muccioli, G., Ghigo, E., & Broglio, F. (2008). Cortistatin-8, a synthetic cortistatin-derived ghrelin receptor ligand, does not modify the endocrine responses to acylated ghrelin or hexarelin in humans. Neuropeptides, 42(1), 89-93.
Prodam F, et al. Cortistatin-8, a Synthetic Cortistatin-derived Ghrelin Receptor Ligand, Does Not Modify the Endocrine Responses to Acylated Ghrelin or Hexarelin in Humans. Neuropeptides. 2008;42(1):89-93. PubMed PMID: 18061663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cortistatin-8, a synthetic cortistatin-derived ghrelin receptor ligand, does not modify the endocrine responses to acylated ghrelin or hexarelin in humans. AU - Prodam,F, AU - Benso,A, AU - Gramaglia,E, AU - Lucatello,B, AU - Riganti,F, AU - van der Lely,A J, AU - Deghenghi,R, AU - Muccioli,G, AU - Ghigo,E, AU - Broglio,F, Y1 - 2007/12/03/ PY - 2007/04/03/received PY - 2007/08/30/revised PY - 2007/09/21/accepted PY - 2007/12/7/pubmed PY - 2008/5/2/medline PY - 2007/12/7/entrez SP - 89 EP - 93 JF - Neuropeptides JO - Neuropeptides VL - 42 IS - 1 N2 - Cortistatin (CST), a neuropeptide with high structural homology with somatostatin (SST), binds all SST receptor (SST-R) subtypes but, unlike SST, also shows high binding affinity to ghrelin receptor (GHS-R1a). CST exerts the same endocrine activities of SST in humans, suggesting that the activation of the SST-R might mask the potential interaction with ghrelin system. CST-8, a synthetic CST-analogue devoid of any binding affinity to SST-R but capable to bind the GHS-R1a, has been reported able to exert antagonistic effects on ghrelin actions either in vitro or in vivo in animals. We studied the effects of CST-8 (2.0 microg/kg i.v. as a bolus or 2.0 microg/kg/h i.v. as infusion) on both spontaneous and ghrelin- or hexarelin- (1.0 microg/kg i.v. as bolus) stimulated GH, PRL, ACTH and cortisol secretion in 6 normal volunteers. During saline, no change occurred in GH and PRL levels while a spontaneous ACTH and cortisol decrease was observed. As expected, both ghrelin and hexarelin stimulated GH, PRL, ACTH and cortisol secretion (p<0.05). CST-8, administered either as bolus or as continuous infusion, did not modify both spontaneous and ghrelin- or hexarelin-stimulated GH, PRL, ACTH and cortisol secretion. In conclusion, CST-8 seems devoid of any modulatory action on either spontaneous or ghrelin-stimulated somatotroph, lactotroph and corticotroph secretion in humans in vivo. These negative results do not per se exclude that, even at these doses, CST-8 might have some neuroendocrine effects after prolonged treatment or that, at higher doses, may be able to effectively antagonize ghrelin action in humans. However, these data strongly suggest that CST-8 is not a promising candidate as GHS-R1a antagonist for human studies to explore the functional interaction between ghrelin and cortistatin systems. SN - 0143-4179 UR - https://www.unboundmedicine.com/medline/citation/18061663/Cortistatin_8_a_synthetic_cortistatin_derived_ghrelin_receptor_ligand_does_not_modify_the_endocrine_responses_to_acylated_ghrelin_or_hexarelin_in_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4179(07)00090-X DB - PRIME DP - Unbound Medicine ER -