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Symbol GHRL contributors: mct/pgu - updated : 09-12-2016
HGNC name ghrelin/obestatin preprohormone
HGNC id 18129
Location 3p25.3      Physical location : 10.327.433 - 10.334.631
Synonym name
  • obestatin
  • ghrelin, growth hormone secretagogue receptor ligand
  • GH releasing acylated peptide
  • growth hormone secretagogue
  • M46 protein
  • motilin related peptide
  • ghrelin O-acyltransferase
  • Synonym symbol(s) MTLRP, GOAT
    TYPE functioning gene
    STRUCTURE 7.20 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor   HRE
    text structure
  • a TATATAA element and putative binding sites for several transcription factors
  • upstream region of the promoter has two additional putative E-box sites, and site-directed mutagenesis (role for upstream stimulatory factor transcription factors in the regulation of ghrelin expression)
  • having a KLF4-responsive region
  • MAPPING cloned Y linked N status provisional
    Map pter - D3S4351 - D3S1317 - GHRL - D3S1335 - D3S1350 - cen
    TRANSCRIPTS type messenger
    text two transcriptional initiation sites: one at -80 and the other at -555 (PMID: 19327128)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 549 - 116 - 2007 17727735
    4 - 501 - 105 - 2007 17727735
    4 - 498 - 104 - 2007 17727735
    3 - 384 - 66 - 2007 17727735
    5 - 552 - 117 - 2007 17727735
    6 - 910 - 116 - 2007 17727735
    5 - 638 - 117 - 2007 17727735
    6 - 835 - 117 - 2007 17727735
    6 - 913 - 117 - 2007 17727735
    7 - 1125 - 117 - 2007 17727735
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly Homo sapiens
    Endocrineadrenal gland   highly Homo sapiens
     neuroendocrinepituitary  predominantly Homo sapiens
     pancreas   highly Homo sapiens
    Reproductivefemale systemovary  highly Homo sapiens
     male systemprostate    Homo sapiens
     male systemmale genital tract    Homo sapiens
     male systemseminal vesicles    Homo sapiens
     male systemtestis    Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine  Homo sapiens
    Muscularstriatumskeletal   Mus musculus
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines choriocarcinoma
    at STAGE
    physiological period embryo, pregnancy
    Text placenta
    isoforms Precursor two sequences of the 28AAs peptide in the precursor
    interspecies homolog to rattus Ghrelin
    ortholog to murine motilin-related peptide (Mtlrp)
  • motilin family
  • CATEGORY regulatory , signaling hormone
    basic FUNCTION
  • involved in the hypothalamic regulation of energy homeostasis (and regulation of feeding)
  • regulating GH release, growth hormone receptor ligand and stimulating insulin secretion
  • ghrelin secretion predicts bone density independent of body composition, the GH-IGF-I axis, cortisol, or estradiol in healthy girls but not in those with anorexia nervosa
  • may play an important role as vasodilator local hormones and regulation of blood pressure during hemodialysis
  • circulating appetite-inducing hormone activity
  • metabolic hormone capable of binding to GPR39 to regulate the functions of diverse gastrointestinal and adipose tissues
  • orexigenic hormone that is secreted from the stomach during fasting, stimulates the release of GH (growth hormone) from the pituitary gland and regulates both food intake and energy balance
  • relaxing agent of iris dilator and sphincter muscles
  • may play a role in appetite regulation in patients with impaired glucose regulation (IGR) and type 2 diabetes mellitus (T2DM)
  • involvement of obestatin signalling in glucose homeostasis and T2DM development
  • involved in inhibiting thirst and anxiety, improving memory, regulating sleep, affecting cell proliferation, and increasing the secretion of pancreatic juice enzymes
  • induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver
  • in liver may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation
  • increased beta-cell cAMP and activated extracellular signal-related kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI 3-kinase)/Akt
  • promotes beta-cell and islet cell survival and stimulates the expression of main regulatory beta-cell genes, identifying a new role for this peptide within the endocrine pancreas
  • significantly decreased proliferation and induced apoptosis
  • stimulates exploratory sniffing and increases olfactory sensitivity, presumably enhancing the ability to locate, identify, and select foods
  • role of ghrelin in the regulation of energy balance and cardiovascular function
  • negative correlation between active ghrelin levels and birth weight in preterm infants
  • role in suppression of gut-derived satiety signals
  • role of obestatin in the regulation of myogenesis in adult skeletal muscle
  • GHRL/GPR39 system is involved in myogenesis and GHRL is expressed by differentiating myogenic precursors to function in an autocrine manner
  • exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition CPT1A
  • in addition to formerly reported mechanisms, GHRL also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity
  • role as a circulating orexigenic signal, but has also been found to be involved in the modulation of glucose homeostasis
  • endogenous ligand for the growth hormone secretagogue receptor, produced predominantly in the stomach
  • regulate neurogenesis in the hippocampus
  • peptide mainly produced by the stomach and released into circulation, affecting energy balance and growth hormone release
  • GHRL, and LEP play an important role in the maintenance of the balance of IL17-producing and T-regulatory cells during pregnancy
  • does likely not play a crucial role in feeding behavior, but rather is involved in maintaining body weight
  • may exert its effects by influencing the functional status of different cell types in the gastric muscle layer to subsequently enhance the contractive effect of cholinergic neurotransmitters and enhance gastric motilit
  • circulating ghrelin levels are under the control of both acute and chronic energy status: at the acute scale, ghrelin levels are increased by fasting and decreased by feeding, whereas at the chronic scale, they are high in obese subjects and low in lean subject
  • plays an inhibitory role in the development of hypothalamic neural circuits, suggesting that proper expression of ghrelin during neonatal life is pivotal for lifelong metabolic regulation
  • plays an autocrine modulatory role in fetal neural development
  • plays a beneficial role in multiple processes of atherogenesis and vascular function (pMID: 26103606)
  • is a brain-gut peptide that regulates gastrointestinal (GI) motility
  • positively regulates GI motility by exciting both central and enteric neurons, including those of the paraventricular nucleus (PVN), by activating growth hormone secretagogue receptor (GHSR) and central neuropeptide Y (NPY) pathways, and peripheral muscarinic acetylcholine receptors
  • plasma ghrelin is likely affected by stress
  • ghrelin secretion appears to be intensely responsive to both acute and chronic stress
  • is an octanoylated peptide hormone that plays a key role in the regulation of the body weight and glucose homeostasis
  • ghrelin binds to serum ALB and this interaction impacts on the biological activity of the hormone
    metabolism energetic
    a component
  • basic helix/loop/helix transcription factors USF1 and USF2 specifically bind to E-boxes in the promoter as a heterodimer, and may play a role in the regulation of expression
    small molecule
  • leptin (to feeding regulation)
  • ligand for the growth hormone secretagogue receptor GHSR
  • interact with the G protein-coupled receptor, GPR39
  • is the strongest GH1 secretagogue and may be a key regulator of GH1 peak amplitude
  • GHRL is the ligand for the orphan receptor GPR39, which belongs to the family of the ghrelin and motilin receptors
  • TP53 is necessary for the actions of GHRL on white adipose tissue (WAT) and liver, leading to changes in expression levels of lipogenic and adipogenic genes, and modifying body weight
  • FFAR4 inducing decrease of GHRL secretion after feeding, by acting directly on gastric FFAR4-expressing ghrelin cells
  • NKX2.2, a homeodomain-containing transcription factor that is important for GHRL cell development in pancreas, activates the promoter activity
  • PORCN, HHAT and GHRL have been shown to acylate specific proteins or peptides
  • ALB-GHRL interaction reduces the spontaneous deacylation of the hormone
  • ETV5 could transactivate GHRL promoter region and increase its expression, leading to subsequent increase in the production of acyl ghrelin
  • cell & other
    repressed by PAX4
    decrease of GHRL secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric FFAR4-expressing GHRL cells
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    plasma ghrelin levels in children with PWS are elevated at any age, including during the first years of life, thus preceding the development of obesity
    constitutional     --low  
    low expression of ghrelin and GH, without causal relationship in obesity, and decreases under conditions of positive energy balance, such as feeding, hyperglycaemia and obesity
    constitutional     --low  
    in impaired glucose regulation (IGR) and type 2 diabetes mellitus (T2DM)
    constitutional     --over  
    increases under conditions of negative energy balance, such as starvation, cachexia and anorexia nervosa
    tumoral     --over  
    in modified prostatic epithelial cells (both hyperplastic or neoplastic) express higher levels of ghrelin than normal prostate
    constitutional     --low  
    in heart failure
    constitutional     --over  
    were associated with an increased risk of Barrett esophagus
    constitutional     --over  
    in young children with Prader-Willi Syndrome long before the onset of hyperphagia, especially during the early phase of poor appetite and feeding
    constitutional     --over  
    in children with growth hormone deficiency and neurosecretory dysfunction
    Variant & Polymorphism
    Candidate gene
    Therapy target
    application of specific inhibitors that block ghrelin signaling might provide new avenues for the design of better adjunctive therapies for prostate cancer
    may provide a novel therapeutic strategy for the treatment of disorders related to synaptic impairment
    potential role of GHRL/GPR39 for use as a therapeutic agent for the treatment of trauma-induced muscle injuries or skeletal muscle myopathies