Neuroendocrine and peripheral activities of ghrelin: implications in metabolism and obesity

Ghrelin, a 28-amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity mediated by the hypothalamus-pituitary GH secretagogue (GHS)-receptors specific for synthetic GHS. The discovery of ghrelin definitely changes our understanding of GH regulation but it is also already clear that ghrelin is much more than simply a natural GHS. Ghrelin acts also on other central and peripheral receptors and shows other actions including stimulation of lactotroph and corticotroph secretion, orexia, influence on gastro-entero-pancreatic functions, metabolic, cardiovascular and anti-proliferative effects. GHS were born more than 20 years ago as synthetic molecules suggesting the option that GH deficiency could be treated by orally active GHS as an alternative to recombinant human GH (rhGH). Up to now, this has not been the case and also their usefulness as anabolic anti-aging intervention restoring GH/insulin-like growth factor-I axis in somatopause is still unclear. We are now confronted with the theoretical possibility that GHS analogues could become candidate drugs for treatment of pathophysiological conditions in internal medicine totally unrelated to disorders of GH secretion. Particularly, GHS receptor agonists or antagonists acting on appetite could represent new drug intervention in eating disorders.