Cortistatin (CST) shares high structural homology with somatostatin (SST) and binds all SST-receptors (SST-R) subtypes with similar affinity. However, CST actions, tissue expression patterns and regulation do not fully overlap with those of SST, and, moreover, CST, but not SST, also binds and activates proadrenomedullin N-terminal peptide receptor (MrgX2) and shows binding affinity to ghrelin receptor (GHS-R1a). Several studies performed to clarify the endocrine actions of CST, compared with SST, showed that, in humans, CST and SST share the same endocrine actions, i.e. inhibition of GH and insulin secretion in physiological conditions and in acromegaly. A similar inhibitory effect on PRL and ACTH secretion was shown in acromegaly, prolactinoma or in Cushing's disease. This identity of endocrine actions by CST and SST suggests that SST-R activation by CST overrides any other independent action of this peptide mediated by other receptors. Thus, in terms of endocrine actions, CST can well be considered a natural alternative to SST.