Ghrelin and anterior pituitary function

Ghrelin, a 28 amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a GH Secretagogue Receptor (GHS-R1a). Thus, it was considered as a natural GH secretagogue (GHS) additional to GHRH, although later on ghrelin has mostly been considered a major orexigenic factor. The GH-releasing action of ghrelin takes place both directly on pituitary cells and through modulation of GHRH from the hypothalamus; some functional anti-somatostatin action has also been shown. However, even at the neuroendocrine level, ghrelin is much more than a natural GHS. In fact, it significantly stimulates prolactin secretion in humans, independently of both gender and age and probably involving a direct action on somatomammotroph cells. Above all, ghrelin and synthetic GHS possess an acute stimulatory effect on the activity of the hypothalamic-pituitary-adrenal (HPA) axis in humans, which is, at least, similar to that of the opioid antagonist naloxone, arginine-vasopressin (AVP) and, even, corticotropin-releasing hormone (CRH). Also, ghrelin plays a relevant role in the modulation of the hypothalamic-pituitary-gonadal function, with a predominantly CNS-mediated inhibitory effect upon the gonadotropin pulsatility both in animals and in humans.