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Endocrine Abstracts (2003) 6 S2

Dept Internal Medicine, Univ of Turin, Turin, ITALY.


Ghrelin is a peptide predominantly produced by the stomach although expressed by many other tissues. Its secretion undergoes fluctuations, is stimulated by fasting and energy restriction, reduced by food intake, glucose, insulin and somatostatin. Ghrelin secretion is negatively associated to body mass. Ghrelin was discovered as natural ligand of the GHS1a receptor specific for synthetic GH Secretagogues (GHS); however, ghrelin is much more than a natural GHS. GHS-R1a expression and binding studies have shown GHS-Rs in the hypothalamus-pituitary area but also in other central and peripheral tissues. Like synthetic GHS, besides GH-releasing effect, ghrelin: 1) stimulates lactotroph and corticotroph secretion; 2) has orexigenic activity and modulates energy expenditure; 3) exerts cardiovascular actions; 4) modulates cell proliferation. More recently discovered ghrelin actions are: 5) influence on the gonadal axis; 6) influence on behavior and sleep; 7) control of gastric motility and acid secretion; 8) influence on exocrine/endocrine pancreatic function and glucose metabolism. Ser3-acylation of ghrelin is essential for binding the GHS-R1a and for its endocrine actions. However, both non-acylated and acylated ghrelin bind receptors representing GHS-R subtypes. Moreover, unacylated ghrelin is not fully inactive, exerting cardiovascular activities, modulation of cell proliferation and some metabolic actions. Noteworthy, some GHS-R subtypes are not ghrelin receptors; cardio-vascular receptors specific for peptidyl GHS only mediate actions that are not shared by ghrelin. Clinical perspectives for synthetic ghrelin analogues are under investigation, mostly to clarify whether specific agonists and antagonists would represent a therapeutic approach to obesity and cachexia. Independently of clinical perspectives, it seems of major importance: a) to define the family of GHS-R subtypes mediating the actions of either acylated or unacylated ghrelin; b) to clarify whether ghrelin is 'a' or 'the' natural GHS, i.e.whether another natural ligand of GHS-Rs exists.

Volume 6

194th Meeting of the Society for Endocrinology and Society for Endocrinology joint with Diabetes UK Endocrinology and Diabetes Day

Society for Endocrinology 

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