Endocrine Abstracts (2011) 26 GH1

Ghrelin: a neuroendocrine and/or a metabolic story?

E Ghigo, Turin, Italy

The acylated form of ghrelin (GRLN) was discovered as the natural ligand of the GHS-R1a. GRLN is acylated by a specific octanoyl-transferase (GOAT) and is predominantly produced by the stomach, although expressed by many other endocrine and non-endocrine, peripheral and central tissues. Also GHS-R1is widely expressed by several central and peripheral tissues. Acylated GRLN displays strong GH-releasing activity but is not specific for GH exhibiting other neuroendocrine actions such as stimulation of PRL and ACTH and inhibition of LH. Acylated GRLN is now recognized as a potent orexigenic factor that also modulates energy expenditure as well as other important central functions. At the peripheral level, GRLN modulates gastrointestinal motility and secretion, exerts cardiovascular actions and, most of all, plays major physiological regulation of glucose and lipid metabolism. Acylated GRLN plays a diabetogenic role while non-acylated GRLN (like smaller fragments and its analogues) positively influences glucose and lipid metabolism, as indicated also by recent studies in GOAT KO mice. GRLN receptors different from GHS-R1a are likely to mediate the metabolic actions of non acylated GRLN. In all, acylated and non acylated GRLN, but also obestatin, another relevant product of the GRLN gene, play a major role in regulating peripheral metabolism and it is not by chance that their secretion is mostly under metabolic regulation.

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