Ghrelin is a hormone produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone leptin, produced by adipose tissue, which induces satiation when present at higher levels. In some bariatric procedures, the level of ghrelin is reduced in patients, thus causing satiation before it would normally occur.
Ghrelin is also produced in the hypothalamic arcuate nucleus, where it stimulates the secretion of growth hormone from the anterior pituitary gland.. Receptors for ghrelin are expressed by neurons in the arcuate nucleus and the lateral hypothalamus. The ghrelin receptor is a G protein-coupled receptor, formerly known as the GHS receptor (growth hormone secretagogue receptor).
Ghrelin plays a significant role in neurotrophy, particularly in the hippocampus, and is essential for cognitive adaptation to changing environments and the process of learning. Recently, ghrelin has been shown to activate the endothelial isoform of nitric oxide synthase in a pathway that depends on various kinases including Akt.
Ghrelin exists in an endocrinological inactive (pure peptide) and an active (octanoylated) form (Hexatropin). Side chains other than octanoyl have also been observed.
Ghrelin has emerged as the first circulating hunger hormone. Ghrelin and synthetic ghrelin mimetics (the growth hormone secretagogues) increase food intake and increase fat mass by an action exerted at the level of the hypothalamus. They activate cells in the arcuate nucleus that include the orexigenic neuropeptide Y (NPY) neurons. Ghrelin-responsiveness of these neurones is both leptin- and insulin-sensitive.
Ghrelin also activates the mesolimbic cholinergic-dopaminergic reward link, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food, as well as of addictive drugs, such as ethanol.
Recently, Scripps research scientists have developed an anti-obesity vaccine, which is directed against the hormone ghrelin. The vaccine uses the immune system, specifically antibodies, to bind to selected targets, directing the body's own immune response against them. This prevents ghrelin from reaching the central nervous system, thus producing a desired reduction in weight gain.
The discovery of ghrelin was reported by Masayasu Kojima and colleagues in 1999. The name is based on its role as a ''growth hormone-releasing peptide'', with reference to the Proto-Indo-European root ''ghre'', meaning ''to grow''. The name can also be viewed as an interesting (and incidental) pun, too, as the initial letters of the phrase ''growth hormone-releasing'' give us "ghre" with "lin" as a usual suffix for some hormones.
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