Ghrelin: what do we know about its role in health and disease?

Ghrelin is a 28 amino acid peptide predominantly produced by the stomach that has been discovered to be a natural ligand of the orphan growth hormone (GH) secretagogue (GHS) receptor (GHS-R) type 1a. Like synthetic GHS, ghrelin possesses a strong GH-releasing effect provided that the molecule is acylated in serine3 and it is thought to be a natural GHS of major importance in the control of somatotropic function1,2. Evidence that GHS-R are expressed in the hypothalamus-pituitary unit as well as in many other areas of the central nervous system and in peripheral endocrine and non-endocrine tissues pointed to other endocrine and non-endocrine actions. Indeed ghrelin is now recognized as a major new orexigenic factor. However, again, there is evidence indicating that it is more than simply a natural GHS and an orexigenic factor. In particular, the hypothesis that acylated ghrelin is the only active form, specifically acting by activation of GHS-R1a, already seems to have been overridden; the existence of GHS-R subtypes and results showing that non-acylated ghrelin is an active molecule are reasonably clear. Therefore, the roles and perspectives for ghrelin in health and disease will be briefly considered.