Appetite-regulating hormone is the peptide precursor of ghrelin the ligand for the growth hormone secretagogue receptor type 1 (GHSR). It is coded by the GHRL gene at 3p26-p25. After O-octanoylation or O-decanoylation it is actually cleaved into:
- Ghrelin-28 (Ghrelin)
- Stimulates growth hormone production.
- Also has actions within the gastrointestinal system (produced by the stomach and pancreas - ε cells) that favour hunger, including increasing gastric emptying.
- Levels abnormally raised in Prader-Willi syndrome.
- This has amidation of Leu-98
- Involved in satiety and decreased food intake
- Ligand for the orphan G protein-coupled receptor GPR39
Secretion occurs before meals, and decrease after them.
Its actions cause the release of growth hormone with stimulation of appetite, induction of adiposity and stimulation of gastric acid secretion. Ghrelin receptors are expressed in the hypothalamus, hippocampus, ventral tegmental area (VTA) and laterodorsal tegmental area (LTA)
It has been suggested that at least in mice ghrelin may affect alcohol dependence.. This is early work which is not shown to apply to primates, and the effect of blocking this hormone system remains speculative. None the less the modulation of the cholinergic-dopaminergic reward link is an attractive therapeutic target and certainly work is on going with the subtypes of acetylcholine receptor implicated. However in man hyperghrelinaemia is associated with the obesity of Prader-Willi syndrome, although not normal obesity in childhood and with alcohol dependence.
- ↑ Jerlhag E, Egecioglu E, Landgren S, Salomé N, Heilig M, Moechars D, Datta R, Perrissoud D, Dickson SL, Engel JA. Requirement of central ghrelin signaling for alcohol reward. Proceedings of the National Academy of Sciences of the United States of America. 2009 Jul 7; 106(27):11318-23.(Link to article – subscription may be required.)
- ↑ Jerlhag E, Egecioglu E, Dickson SL, Svensson L, Engel JA. Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2008 Jul; 18(7):508-18.(Link to article – subscription may be required.)
- ↑ Feigerlová E, Diene G, Conte-Auriol F, Molinas C, Gennero I, Salles JP, Arnaud C, Tauber M. Hyperghrelinemia precedes obesity in Prader-Willi syndrome. The Journal of clinical endocrinology and metabolism. 2008 Jul; 93(7):2800-5.(Link to article – subscription may be required.)
- ↑ Haqq AM, Farooqi IS, O'Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, LaFranchi SH, Purnell JQ. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. The Journal of clinical endocrinology and metabolism. 2003 Jan; 88(1):174-8.
- ↑ Kraus T, Schanze A, Gröschl M, Bayerlein K, Hillemacher T, Reulbach U, Kornhuber J, Bleich S. Ghrelin levels are increased in alcoholism. Alcoholism, clinical and experimental research. 2005 Dec; 29(12):2154-7.
- ↑ Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9; 402(6762):656-60.(Link to article – subscription may be required.)