| Primary Identifier | IPR005441 | Type | Family |
| Short Name | Preproghrelin |
| description | Growth hormone (GH) is a pituitary hormone involved in cell and overall bodygrowth, carbohydrate-protein-lipid metabolism and osmotic homeostasis.Control of GH release was initially ascribed to 2 pathways: stimulation byhypothalamic GH-releasing hormone (GHRH) and inhibition by somatostatin.More recently, synthetic compounds, termed GH secretagogues (GHS), were shown to stimulate GH release strongly. This effect is elicited by an orphanG protein-coupled receptor (GPCR), subsequently named the GHS receptor(GHS-R). The endogenous ligand for this receptor was purified from rat andhuman stomach and named ghrelin [].The purified cDNA for ghrelin encodes a 117 amino acid prepropeptide. Thefirst 23 amino acid residues form a signal peptide that is cleaved to leaveproghrelin. Residues 24-51 are cleaved to yield active ghrelin, discardingthe C-terminal fragment []. The 28-residue ghrelin peptide that is left is biologically inactive. Esterification with n-octanoic acid at Ser3 is required for biological activity. Ghrelin mRNA is expressed mainly in thestomach in a distinct endocrine cell type in the submucosal layer, known asX/A-like cells. The active peptide is secreted into the bloodstream ratherthan the stomach. Ghrelin responsive cells are found in abundance in a limited area of the hypothalamic arcuate nucleus (ARC), a region involved incontrol of food intake. As well as releasing GH indirectly via its action on the ARC region of the hypothalamus, ghrelin also appears to be able tostimulate GH release via direct action on the pituitary [].A further variant of the ghrelin peptide exists in rat stomach, des-Gln14-ghrelin. This is produced by alternative splicing and does not require theesterification by n-octanoic acid for biological activity. However, its presence in only small quantities in the stomach suggests ghrelin is themajor active form. The ghrelin active peptide and the GHS receptor sharesequence similarity with motilin and the motilin receptor, respectively, suggesting an evolutionary relationship. |
