Endocrine and metabolic actions of ghrelin.

The acylated form of ghrelin (GRLN) has been discovered as the natural ligand of the GH secretagogue (GHS) receptor-1a (GHS-R1a). This peptide, whose acylation is performed by a specific octanoyl-transferase, is predominantly produced by the stomach, although expressed by many other endocrine and nonendocrine, peripheral and central tissues. Also GHS-R1a shows wide distribution, being distributed in several central and peripheral tissues. GRLN displays strong GH-releasing activity but its action is not specific for GH exhibiting other neuroendocrine activities such as stimulation of PRL and ACTH and inhibition of LH. GRLN is now mostly recognized as a potent orexigenic factor stimulating food intake and modulating energy expenditure. At the peripheral level, GRLN modulates gastrointestinal motility and secretion and also exerts cardiovascular actions. Mostly, at the peripheral level, GRLN exerts probably its major physiological action regulating glucose and lipid metabolism. In fact, GRLN in its acylated form has a diabetogenic action while in its non-acylated form it has a favorable influence on glucose, lipid metabolism and insulin sensitivity as well as the inhibition of lipolysis. GRLN receptors have been well demonstrated either in the endocrine pancreas or the adipose tissue; at these levels there are receptors that bind GRLN independently of its acylation (therefore a non-GHS-R1a, still undefined receptor). In all, the products of the GRLN gene, i.e. acylated and nonacylated GRLN, as well as obestatin, play a major role in regulating peripheral metabolism and it is not by chance that their secretion is mostly under metabolic regulation. Copyright 2010 S. Karger AG, Basel.