Ghrelin in the regulation of GH secretion and other pituitary hormones.

Ghrelin, a 28 amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a growth hormone (GH) secretagogue receptor (GHS-R1a). Thus, it was considered as a natural GHS additional to growth hormone-releasing hormone (GHRH), although later on ghrelin has mostly been considered a major orexigenic factor. Ghrelin activity at the pituitary level is not fully specific for GH, because it also includes stimulatory effects on both the lactotroph and corticotroph system. In fact, ghrelin in humans significantly stimulates prolactin (PRL) secretion, independently of both gender and age and probably involving a direct action on somatomammotroph cells, and possess an acute stimulatory effect on the activity of the hypothalamus-pituitary-adrenal axis, which is similar to that of the opioid antagonist naloxone, arginine-vasopressin (AVP) and, even, corticotropin-releasing hormone (CRH). Finally, ghrelin plays a relevant role in the modulation of the hypothalamus-pituitary-gonadal axis function, with a predominantly central nervous system (CNS)-mediated inhibitory effect upon the gonadotropin pulsatility both in animals and in humans. Overall, ghrelin is a pleiotropic hormone with a wide spectrum of biological actions. Further studies are required to gain insights into the exact mechanisms involved in ghrelin physiology and pathophysiology and to define the potential therapeutic roles, if any, of ghrelin and its analogs.