ghrelin ghrelin ghrelin (/ˈɡrɛlɪn/; or lenomorelin, inn) is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid. ghrlavailable structurespdbortholog search: pdbe rcsb list of pdb id codes1p7x,%%s2jsh, 2jsi, 2jsjidentifiersaliasesghrl, ghrelin, ghrelin, ghrelin and obestatin prepropeptide, mtlrpexternal idsomim: 605353 mgi: 1930008 homologene: 9487 genecards: ghrl gene location (human)chr.chromosome 3 (human)band3p25.3start10,285,666 bpend10,292,947 bpgene location (mouse)chr.chromosome 6 (mouse)band6 e3|6 52.84 cmstart113,693,080 bpend113,696,841 bprna expression patternbgeehumanmouse (ortholog)top expressed incardiabody of stomachpancreatic epithelial cellfundusbone marrow cellspancreatic ductal cellislet of langerhansduodenumbloodsural nervetop expressed inepithelium of stomachpyloric antrummucous cell of stomachduodenumspermatidspermatocytesuperior frontal gyruslipjejunumyolk sacmore reference expression databiogpsn/agene ontologymolecular function protein tyrosine kinase activator activity hormone activity protein binding ghrelin receptor binding g protein-coupled receptor binding growth hormone-releasing hormone activity cellular component postsynapse cytoplasm endoplasmic reticulum lumen extracellular region axon secretory granule lumen extracellular space schaffer collateral - ca1 synapse glutamatergic synapse biological process positive regulation of appetite g protein-coupled receptor signaling pathway positive regulation of cortisol secretion positive regulation of growth hormone receptor signaling pathway negative regulation of insulin secretion gastric acid secretion positive regulation of cytosolic calcium ion concentration dendrite development regulation of response to food negative regulation of apoptotic process positive regulation of corticotropin secretion negative regulation of locomotion cortisol secretion response to estrogen negative regulation of endothelial cell proliferation positive regulation of circadian sleep/wake cycle, non-rem sleep cartilage development decidualization regulation of cell population proliferation growth hormone secretion positive regulation of growth hormone secretion excitatory postsynaptic potential hormone-mediated signaling pathway glucose metabolic process positive regulation of multicellular organism growth negative regulation of angiogenesis response to hormone actin polymerization or depolymerization positive regulation of response to food negative regulation of circadian sleep/wake cycle, rem sleep negative regulation of inflammatory response positive regulation of insulin secretion positive regulation of synapse assembly positive regulation of protein tyrosine kinase activity adult feeding behavior response to nutrient levels positive regulation of eating behavior positive regulation of adipose tissue development negative regulation of interleukin-1 beta production gastric emptying positive regulation of insulin secretion involved in cellular response to glucose stimulus positive regulation of growth response to electrical stimulus regulation of transmission of nerve impulse positive regulation of bone development positive regulation of sprouting angiogenesis positive regulation of gastro-intestinal system smooth muscle contraction positive regulation of small intestine smooth muscle contraction regulation of gastric motility positive regulation of vascular endothelial cell proliferation positive regulation of growth rate positive regulation of small intestinal transit positive regulation of gastric mucosal blood circulation positive regulation of feeding behavior regulation of signaling receptor activity energy homeostasis postsynaptic modulation of chemical synaptic transmission regulation of postsynapse organization positive regulation of cold-induced thermogenesis sources:amigo / quickgoorthologsspecieshumanmouseentrez5173858991ensemblensg00000157017ensmusg00000064177uniprotq9ubu3q9eqx0refseq (mrna)nm_001134941nm_001134944nm_001134945nm_001134946nm_001302821nm_001302822nm_001302823nm_001302824nm_001302825nm_016362nm_021488nm_001286404nm_001286405nm_001286406nm_001379129refseq (protein)np_001128413np_001128416np_001128417np_001128418np_001289750np_001289751np_001289752np_001289753np_001289754np_057446np_001128413np_001128416np_001128417np_001128418np_001289750np_001289751np_001289752np_001289753np_001289754np_057446np_001273333np_001273334np_001273335np_067463np_001366058location (ucsc)chr 3: 10.29 – 10.29 mbchr 6: 113.69 – 113.7 mbpubmed searchwikidataview/edit humanview/edit mouse ghrelin activates cells in the anterior pituitary gland and hypothalamic arcuate nucleus, including neuropeptide y neurons that initiate appetite. ghrelin stimulates brain structures having a specific receptor – the growth hormone secretagogue receptor 1a (ghsr-1a). ghrelin also participates in regulation of reward cognition, learning and memory, the sleep-wake cycle, taste sensation, reward behavior, and glucose metabolism. history and name ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1a receptor or ghs-r) was determined in 1999. the hormone name is based on its role as a growth hormone-releasing peptide, with reference to the proto-indo-european root gʰre-, meaning "to grow". gene, transcription products, and structure preproghrelin (green and blue) and ghrelin (green). the ghrl gene produces mrna which has four exons. five products arise: the first is the 117-amino acid preproghrelin. it is homologous to promotilin; both are members of the motilin family. it is cleaved to produce proghrelin which is cleaved to produce an unacylated 28-amino acid ghrelin and an acylated c-ghrelin. obestatin is presumed to be cleaved from c-ghrelin. ghrelin only becomes active when caprylic (octanoic) acid is linked posttranslationally to serine at the 3-position by the enzyme ghrelin o-acyltransferase (goat) to form a proteolipid. it is located on the cell membrane of ghrelin cells in the stomach and pancreas. the non-octanoylated form is desacyl ghrelin. it does not activate the ghs-r receptor but does have other effects: cardiac, anti-ghrelin, appetite stimulation, and inhibition of hepatic glucose output. side-chains other than octanoyl have also been observed: these can also trigger the ghrelin receptor. in particular, decanoyl ghrelin has been found to constitute a significant portion of circulating ghrelin in mice, but as of 2011 its presence in humans has not been established. ghrelin cells alternative names the ghrelin cell is also known as an a-like cell (pancreas), x-cell (for unknown function), x/a-like cell (rats), epsilon cell (pancreas), p/d sub 1 cell (humans) and gr cell (abbreviation for ghrelin cell). location ghrelin cells are found mainly in the stomach and duodenum, but also in the jejunum, lungs, pancreatic islets, gonads, adrenal cortex, placenta, and kidney. it has also been shown that ghrelin is produced locally in the brain. ghrelin cells are also found in oxyntic glands (20% of cells), pyloric glands, and small intestine. features they are ovoid cells with granules. they have gastrin receptors. some produce nesfatin-1. ghrelin cells are not terminally differentiated in the pancreas: they are progenitor cells that can give rise to a-cells, pp cells and beta-cells there. function and mechanism of action ghrelin is a participant in regulating the complex process of energy homeostasis which adjusts both energy input – by adjusting hunger signals – and energy output – by adjusting the proportion of energy going to atp production, fat storage, glycogen storage, and short-term heat loss. the net result of these processes is reflected in body weight, and is under continuous monitoring and adjustment based on metabolic signals and needs. at any given moment in time, it may be in equilibrium or disequilibrium. gastric-brain communication is an essential part of energy homeostasis, and several communication pathways are probable, including the gastric intracellular mtor/s6k1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems, and both afferent and efferent vagal signals. ghrelin and synthetic ghrelin mimetics (growth hormone secretagogues) increase body weight and fat mass by triggering receptors in the arcuate nucleus that include neuropeptide y (npy) and agouti-related protein (agrp) neurons. ghrelin-responsiveness of these neurons is both leptin- and insulin-sensitive. ghrelin reduces the sensitivity of gastric vagal afferents, so they are less sensitive to gastric distension. in addition to its function in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic reward link in inputs to the ventral tegmental area and in the mesolimbic pathway, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food and addictive drugs such as ethanol. ghrelin receptors are located on neurons in this circuit. hypothalamic ghrelin signalling is required for reward from alcohol and palatable/rewarding foods. ghrelin has been linked to inducing appetite and feeding behaviors. circulating ghrelin levels are the highest right before a meal and the lowest right after. injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner. so the more ghrelin that is injected the more food that is consumed. however, ghrelin does not increase meal size, only meal number. ghrelin injections also increase an animal's motivation to seek out food, behaviors including increased sniffing, foraging for food, and hoarding food. body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. studies have shown that ghrelin levels are positively correlated with weight. this data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain. blood levels blood levels are in the pmol/l or fmol/ml range. both active and total ghrelin can be measured. circulating ghrelin concentrations rise before eating and fall afterward, more strongly in response to protein and carbohydrate than to lipids. the plasma ghrelin-like immunoreactivity concentration measured with a particular radioimmunoassay in a typical human is 166.0 + 10.1 fmol/ml. serum ghrelin concentrations tend to increase in age and vary throughout the day, with values peaking while one is asleep. ghrelin receptor the ghrelin receptor ghs-r1a (a splice-variant of the growth hormone secretagogue receptor, with the ghs-r1b splice being inactive) is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase in hunger, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. they are present in high density in the hypothalamus and pituitary, on the vagus nerve (on both afferent cell bodies and efferent nerve endings) and throughout the gastrointestinal tract. locations of action glucose metabolism the entire ghrelin system (dag, ag, ghs-r and goat) has a gluco-regulatory action. sleep preliminary research indicates that ghrelin participates in the regulation of circadian rhythms. a review reported finding strong evidence that sleep restriction affected ghrelin or leptin levels, or energy expenditure. reproductive system ghrelin has inhibitory effects on gonadotropin-releasing hormone (gnrh) secretion. it may cause decreased fertility. fetus and neonate ghrelin is produced early by the fetal lung and promotes lung growth. umbilical cord blood levels of ghrelin show a correlation between ghrelin levels and birth weight. anorexia and obesity ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals, suggesting that ghrelin does not contribute to obesity, except in the cases of prader–willi syndrome-induced obesity, where high ghrelin levels are correlated with increased food intake. those with anorexia nervosa have high plasma levels of ghrelin compared to both the constitutionally thin and normal-weight controls. the level of ghrelin increases during the time of day from midnight to dawn in thinner people, which suggests there is a flaw in the circadian rhythm of obese individuals. ghrelin levels are high in people with cancer-induced cachexia. there is insufficient evidence to conclude either for or against use of ghrelin in managing cachexia associated with cancer. disease management gastric bypass surgery gastric bypass surgery not only reduces gut capacity for food, but also lowers ghrelin levels compared to both lean people and those who lost weight through dieting. studies have not clarified whether ghrelin levels return to normal in people who had gastric bypass surgery after weight loss has stabilized. gastric bypass surgery involving vertical-sleeve gastrectomy reduces plasma ghrelin levels by about 60% in the long term.