Letters to Nature

Nature 402, 656-660 (9 December 1999) | doi:10.1038/45230; Received 21 July 1999; Accepted 7 October 1999

Ghrelin is a growth-hormone-releasing acylated peptide from stomach

Masayasu Kojima1, Hiroshi Hosoda1, Yukari Date1, Masamitsu Nakazato2, Hisayuki Matsuo1 & Kenji Kangawa1

  1. Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka 565-8565, Japan
  2. Third Department of Internal Medicine, Miyazaki Medical College, Miyazaki 889-1692, Japan

Correspondence to: Masayasu Kojima1 Correspondence and requests for materials should be addressed to K.K. (e-mail: Email: kangawa@ri.ncvc.go.jp). The nucleotide sequence data reported here will appear in the DDBJ/EMBL/GenBank nucleotide sequence databases with the accession numbers AB029433 (rat) and AB029434 (human).

Small synthetic molecules called growth-hormone secretagogues (GHSs)1, 2, 3 stimulate the release of growth hormone (GH) from the pituitary4, 5. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R6, 7 strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH)4, 5. We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide 'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.