Natural and synthetic growth hormone secretagogues: do they have therapeutic potential?

Ghrelin, a 28 amino acid-acylated peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity. It is mediated by the hypothalamic-pituitary GH secretagogue (GHS) receptors, which are specific to a family of synthetic, orally active molecules known as GHSs. However, despite their potent and reproducible GH-releasing activity, the potential clinical use of GHSs as orally active growth-promoting agents or anabolic anti-aging drugs has not been confirmed. Ghrelin and GHSs also exert other actions mediated through central and peripheral receptors, including stimulation of adrenocorticotrophic hormone and prolactin secretion, influence on insulin secretion and glucose metabolism, orexigenic effects and modulatory activity on the neuroendocrine and metabolic response to starvation, influence on exocrine gastro-entero-pancreatic functions, cardiovascular effects and modulation of cell proliferation and apoptosis. The discovery of ghrelin and the characterization of these GH-independent biological activities has widened the knowledge of some critical aspects of neuroendocrinology and suggests possible roles for GHSs and ghrelin in the treatment of pathophysiological conditions, including those unrelated to disorders of GH secretion.