Alessandro Laviano, Alessio Molfino, Serena Rianda and Filippo Rossi Fanelli Pages 4749 - 4754 ( 6 )
The growth hormone secretagogue receptor (GHS-R) is a component of the ghrelin signaling pathway and is involved in mediating the pleiotropic effects of ghrelin. Two isoforms have been identified, but only GHS-R1a binds with acyl ghrelin and transduces its message. However, the inactive variant of GHS-R, GHS-R1b, appears to play a critical role in modulating the activity of GHS-R1a by forming heterodimeric complexes which attenuates trafficking of the active variant to the cell surface. The molecular mechanisms of signal transduction are complex and are specific of the tissues where GHS-R1a is expressed. The potent induction of GH secretion and the stimulation of appetite are the most intensively studied functions of GHS-R1a. However, the tissue distribution of GHS-R1a extends beyond the pituitary and the hypothalamus, and reflects the different biological functions of the ghrelin/GHS-R system. GHS-R1a is also expressed in other brain areas, in the pancreas, adipose tissue, immune cells and cardiovascular system, and modulates learning and memory, glucose and lipid metabolism, inflammatory response and cardiac performance. The pleiotropic effects of the ghrelin/GHS-R system suggest their exploitation to prevent and treat a number of clinical conditions. Among many other syndromes and diseases, cancer cachexia, aging related cognitive decline, obesity and diabetes may significantly benefit from the use of GHS-R1a agonists or antagonists.
GHS-R1a, GHS-R1b, hypothalamus, ghrelin, GH, appetite, obesity, diabetes, inflammatory response, antagonists.
Department of Clinical Medicine, Sapienza University, viale dell’Universita 37, 00185 Rome, Italy.