Study summary · research use only
Cortistatin-8, a synthetic cortistatin-derived ghrelin receptor ligand, does not modify the endocrine responses to acylated ghrelin or hexarelin in humans
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this human study, the authors tested cortistatin-8 (CST-8), a synthetic cortistatin-derived ghrelin receptor ligand, on endocrine responses in 6 normal volunteers. CST-8 was given at 2.0 microg/kg i.v. as a bolus or 2.0 microg/kg/h as infusion, with or without ghrelin- or hexarelin- (1.0 microg/kg i.v.) stimulation, and GH, PRL, ACTH, and cortisol secretion were measured. During saline, GH and PRL were unchanged and a spontaneous ACTH and cortisol decrease occurred. Both ghrelin and hexarelin stimulated GH, PRL, ACTH, and cortisol (p<0.05). CST-8, as bolus or infusion, did not modify spontaneous or ghrelin-/hexarelin-stimulated secretion. The authors conclude CST-8 seemed devoid of modulatory action at these doses and is not a promising GHS-R1a antagonist candidate for human studies, without excluding effects at higher doses or with prolonged treatment.
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.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.