Endocrine Abstracts (2007) 14 P561

Effects of CST-8, a synthetic cortistatin analogue, in humans

Andrea Benso1, Flavia Prodam1, Elena Gramaglia1, Fabrizio Riganti1, Barbara Lucatello1, Aart Jan van der Lely2, Romano Deghenghi1, Giampiero Muccioli3, Ezio Ghigo1 & Fabio Broglio1

1Div Endocrinology and Metabolic Diseases, Dpt Internal Medicine, University of Turin, Turin, Italy; 2Div Endocrinology, Dpt Internal Medicine, Erasmus University Rotterdam, Rotterdam, Netherlands; 3Dpt Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy.

Cortistatin (CST), a neuropeptide with high structural homology with somatostatin (SS), binds all SS receptor (SS-R) subtypes but, unlike SS, also shows high binding affinity to ghrelin (GRLN) receptor (GRLN-R). In humans CST exerts the same endocrine activities of SS, suggesting that the activation of the SS-R might mask the potential interaction with the GRLN system.

CST-8, a synthetic CST-analogue devoid of any binding affinity to SS-R but capable to bind the GRLN-R, has been reported able to exert antagonistic actions on GRLN actions either in vitro or in vivo in animals. We studied the effects of CST-8 (2.0 μg/kg iv as a bolus or 2.0 μg/kg/h iv as infusion) on both spontaneous and GRLN- or hexarelin (HEX) (1.0 μg/kg iv as bolus)- stimulated GH, PRL, ACTH and cortisol secretion in 6 normal volunteers. The effect of CST-8 iv infusion at 4.0 μg/kg/h on the GH response to GRLN was also studied in 3 subjects. The study was approved by an independent Ethical Committee.

During saline, spontaneous ACTH and cortisol decrease was observed while no change occurred in GH and PRL levels. GRLN and HEX increased (P<0.05) GH, PRL, ACTH and cortisol levels. CST-8 administered either as bolus or as continuous infusion did not modify both spontaneous and GRLN- or HEX-stimulated GH, PRL, ACTH and cortisol secretion. The GH response to GRLN was unchanged even under exposure to the highest CST-8 dose.

In conclusion, CST-8 seems devoid of any modulatory action on either spontaneous or GRLN-stimulated somatotroph, lactotroph and corticotroph secretion. Thus, CST-8 seems an inactive peptide in humans, at least in term of modulation of pituitary hormone secretion.

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