Document Detail


The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake.
MedLine Citation:
PMID:  20456603     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ghrelin and obestatin are two gastrointestinal peptides obtained by post-translational processing of a common precursor, preproghrelin. Ghrelin is an orexigenic and adipogenic peptide and a potent growth hormone secretagogue (GHS) modified by the enzyme ghrelin-O-acyl-transferase to bind and activate its receptor, the GHS-R. The ghrelin/GHS-R pathway is complex and the effects of ghrelin on GH secretion, adiposity and food intake appear to be relayed by distinct mechanisms involving different transduction signals and constitutive activity for the GH-R, different cofactors as modulators of endogenous ghrelin signalling and/or alternative ghrelin receptors. The discovery of obestatin in 2005 brought an additional level of complexity to this fascinating system. Obestatin was initially identified as an anorexigenic peptide and as the cognate ligand for GPR39, but its effect on food intake and its ability to activate GPR39 are still controversial. Although several teams failed to reproduce the anorexigenic actions of obestatin, this peptide has been shown to antagonise GH secretion and food intake induced by ghrelin and could be an interesting pharmacological tool to counteract the actions of ghrelin. Ghrelin and obestatin immunoreactivities are recovered in the blood with an ultradian pulsatility and their concentrations in plasma vary with the nutritional status of the body. It is still a matter of debate whether both hormones are regulated by independent mechanisms and whether obestatin is a physiologically relevant peptide. Nevertheless, a significant number of studies show that the ghrelin/obestatin ratio is modified in anorexia nervosa and obesity. This suggests that the ghrelin/obestatin balance could be essential to adapt the body's response to nutritional challenges. Although measuring ghrelin and obestatin in plasma is challenging because many forms of the peptides circulate, more sensitive and selective assays to detect the different preproghrelin-derived peptides are being developed and may be the key to obtaining a better understanding of their roles in different physiological and pathological conditions.
Authors:
R Hassouna; P Zizzari; V Tolle
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Publication Detail:
Type:  Journal Article; Review     Date:  2010-05-06
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  22     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-21     Completed Date:  2010-11-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  793-804     Citation Subset:  IM    
Affiliation:
UMR894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, 2 ter rue d'Alésia, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Anorexia Nervosa / genetics
Body Composition / physiology*
Eating / physiology*
Ghrelin / genetics,  metabolism*
Growth Hormone / secretion*
Humans
Molecular Sequence Data
Mutation
Nutritional Status
Obesity / metabolism,  physiopathology
Polymorphism, Genetic
Receptors, Ghrelin / antagonists & inhibitors,  genetics,  metabolism
Signal Transduction
Chemical
Reg. No./Substance:
0/Ghrelin; 0/Receptors, Ghrelin; 9002-72-6/Growth Hormone

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