Ghrelin: From somatotrope secretion to new perspectives in the regulation of peripheral metabolic functions

Ghrelin, a peptide predominantly produced by the stomach, has been discovered as natural ligand of the GH secretagogue (GHS) receptor type 1a (GHS-R1a), suggesting the existence a new endogenous modulator of somatotrope secretion. Subsequently, ghrelin turned out to exert pleiotropic actions, consistent with the widespread distribution of ghrelin and GHS-R expression in central and peripheral tissues. Despite that the binding to GHS-R1a requires ghrelin to be acylated in serine 3, some ghrelin actions are independent of such acylation; thus suggesting the possibility of the existence of other GHS-R subtypes. Ghrelin secretion (70% in its unacylated form) is mainly under metabolic control being modulated by glucose, insulin and feeding. On the other hand, ghrelin influences energy metabolism acting both as a central orexigenic factor and directly on the endocrine pancreas, liver and adipose tissue. Recently, another gastric hormone derived from the same ghrelin gene has been isolated and named obestatin. Obestatin in rats resulted in reduced food intake, jejunal contraction and body weight gain, via specific distinct receptors. Thus, all these data indicate that we are exploring a very complex system deeply involved in the modulation of metabolic functions, whose understanding will probably increase our knowledge about diabetes mellitus and the metabolic syndrome.