Growth hormone secretagogues and ghrelin: an update on physiology and clinical relevance

The pulsatile release of growth hormone (GH) by the anterior pituitary is stimulated by small synthetic molecules termed GH secretagogues (GHS). The receptor for GHS (GHS-R) belongs to the family of G-protein-coupled receptors. An endogenous specific ligand of 28 amino acids has recently been purified from rat stomach, it has been termed 'ghrelin'. Ghrelin demonstrates potent and reproducible GH-releasing activity, as well as significant prolactin-, ACTH- and cortisol-releasing activity. However, its major physiological relevance may relate to energy homeostasis. Peripheral daily administration of ghrelin caused weight gain by reducing fat utilization in mice and rats. In man, intravenous ghrelin was shown to stimulate food intake. The pathophysiological role and the potential clinical use of ghrelin are reviewed.