growth hormone secretagogue receptor

成長ホルモン分泌促進因子受容体

WordNet

1. cultivate by growing, often involving improvements by means of agricultural techniques; "The Bordeaux region produces great red wines"; "They produce good ham in Parma"; "We grow wheat here"; "We raise hogs here" (同)raise, farm, produce
2. come to have or undergo a change of (physical features and attributes); "He grew a beard"; "The patient developed abdominal pains"; "I got funny spots all over my body"; "Well-developed breasts" (同)develop, produce, get, acquire
3. become attached by or as if by the process of growth; "The tree trunks had grown together"
4. become larger, greater, or bigger; expand or gain; "The problem grew too large for me"; "Her business grew fast"
5. cause to grow or develop; "He grows vegetables in his backyard"
6. increase in size by natural process; "Corn doesnt grow here"; "In these forests, mushrooms grow under the trees"; "her hair doesnt grow much anymore"
7. (biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children" (同)growing, maturation, development, ontogeny, ontogenesis
8. (pathology) an abnormal proliferation of tissue (as in a tumor)
9. a progression from simpler to more complex forms; "the growth of culture"
10. something grown or growing; "a growth of hair"
11. vegetation that has grown; "a growth of trees"; "the only growth was some salt grass"
12. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
13. the secretion of an endocrine gland that is transmitted by the blood to the tissue on which it has a specific effect (同)endocrine, internal_secretion

PrepTutorEJDIC

1. 『成長する』,育つ,〈植物が〉生える,茂る / (類・量・程などにおいて)『増大する』,大きくなる / 『しだいになる』 / …‘を'成長させる,大きくする,育てる / …から生じる(起こる)
2. 〈U〉(…の)『成長』,発育;『発達』,発展《+『of』+『名』》 / 〈U〉(数・量,重要性・力などの)『増加』,増大,拡張《+『of』+『名』》 / 〈U〉《修飾語[句]を伴って》栽培,生産,…産 / 〈C〉成育した物,(草,木,髪,ひげなどの)生えたもの / 〈C〉腫瘍(しゅよう)
3. =sense organ / 受信装置
4. ホルモン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/06/25 14:24:07」(JST)

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GHSR
Identifiers
Aliases	GHSR, GHDP, growth hormone secretagogue receptor
External IDs	OMIM: 601898 MGI: 2441906 HomoloGene: 57161 GeneCards: GHSR
Gene location (Human) Chr. Chromosome 3 (human) Band 3q26.31 Start 172,445,133 bp End 172,448,456 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3|3 A3 Start 27,371,351 bp End 27,378,010 bp
RNA expression pattern More reference expression data
Gene ontology Molecular function • hormone binding • signal transducer activity • peptide hormone binding • growth hormone-releasing hormone receptor activity • growth hormone secretagogue receptor activity • G-protein coupled receptor activity Cellular component • integral component of membrane • membrane • cell surface • neuron projection • membrane raft • plasma membrane Biological process • negative regulation of interleukin-6 biosynthetic process • negative regulation of interleukin-1 beta production • negative regulation of insulin secretion • regulation of synapse assembly • negative regulation of tumor necrosis factor biosynthetic process • regulation of hindgut contraction • decidualization • positive regulation of insulin-like growth factor receptor signaling pathway • positive regulation of fatty acid metabolic process • hormone-mediated signaling pathway • positive regulation of multicellular organism growth • cellular response to insulin stimulus • response to food • response to hormone • actin polymerization or depolymerization • negative regulation of inflammatory response • signal transduction • positive regulation of appetite • growth hormone secretion • adult feeding behavior • response to growth hormone • positive regulation of eating behavior • spermatogenesis • female pregnancy • learning or memory • negative regulation of norepinephrine secretion • negative regulation of appetite • response to follicle-stimulating hormone • response to estradiol • ghrelin secretion • regulation of transmission of nerve impulse • regulation of growth hormone secretion • cellular response to lipopolysaccharide • response to dexamethasone • negative regulation of locomotion involved in locomotory behavior • cellular response to thyroid hormone stimulus • positive regulation of sprouting angiogenesis • response to monosodium glutamate • negative regulation of tumor necrosis factor secretion • regulation of gastric motility • positive regulation of vascular endothelial cell proliferation • cellular response to insulin-like growth factor stimulus • negative regulation of macrophage apoptotic process • positive regulation of growth • regulation of feeding behavior • positive regulation of small intestinal transit • positive regulation of small intestine smooth muscle contraction • G-protein coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2693	208188
Ensembl	ENSG00000121853	ENSMUSG00000051136
UniProt	Q92847	Q99P50
RefSeq (mRNA)	NM_198407 NM_004122	NM_177330
RefSeq (protein)	NP_004113 NP_940799	NP_796304
Location (UCSC)	Chr 3: 172.45 – 172.45 Mb	Chr 3: 27.37 – 27.38 Mb
PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.

Structure

Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for ghrelin; however, it may function to attenuate activity of isoform 1a.

GHS-R1a falls into G-protein-coupled receptor (GPCR) family. Previous studies have shown that GPCRs can form heterodimers, or functional receptor pairs with other types of G-protein coupled receptors (GPCRs). Various studies suggest that GHS-R1a specifically forms dimers with the following hormone and neurotransmitter receptors: somatostatin receptor 5, dopamine receptor type 2 (DRD2), melanocortin-3 receptor (MC3R), and serotonin receptor type 2C (5-HT_2c receptor). See "Function" section below for details on the purported functions of these heterodimers.

Function

Growth hormone release

The binding of ghrelin to GHS-R1a in pituitary cells stimulates the secretion of growth hormone (GH) by the pituitary gland.

Constitutive activity

One important feature of GHS-R1a is that there is still some activity in the receptor even when it is not actively being stimulated. This is called constitutive activity, and it means that the receptor is always "on," unless acted on by an inverse agonist. This constitutive activity seems to provide a tonic signal required for the development of normal height, probably through an effect on the GH axis. In fact, some genetic variations, or single nucleotide polymorphisms (SNPs), in growth hormone secretagogue receptor, have been found to be associated with hereditary obesity and others with hereditary short stature. It was also found that, when GHS-R1A constitutive activity, was diminished, there were decreased levels of hunger-inducing hormone neuropeptide Y (NPY) as well as in food intake and body weight.

Intracellular signaling mechanisms

When growth hormone secretagogue receptor is activated, a variety of different intracellular signaling cascades can result, depending on the cell type in which the receptor is expressed. These intracellular signaling cascades include mitogen-activated protein kinase (MAPK)), protein kinase A (PKA), protein kinase B (PKB), also known as AKT), and AMP Activated Protein Kinase (AMPK) cascades.

Behavioral reinforcement of food intake

It is well-characterized that activating the growth hormone secretagogue receptor with ghrelin induces an orexigenic state, or general feeling of hunger. However, ghrelin may also play a role in behavioral reinforcement. Studies in animal models, found that food intake increased when ghrelin was specifically administered to just the ventral tegmental area (VTA), a brain area that uses dopamine signaling to reinforce behavior. In fact, the more ghrelin administered, the more food the rodent consumed. This is called a dose-dependent effect. Building on this, it was found that there are growth hormone secretagogue receptors in the VTA and that ghrelin acts on the VTA through these receptors. Current studies, furthermore, suggest that the VTA may contain dimers of GHS-R1a and dopamine receptor type 2 (DRD2). If these two receptors do indeed form dimers, this would somehow link ghrelin signaling to dopaminergic signaling.

Enhancement of learning and memory

The growth hormone secretagogue receptor may also be linked to learning and memory. First of all, the receptor is found in the hippocampus, the brain region responsible for long-term memory. Second, it was found that specifically activating the receptor in just the hippocampus increased both long-term potentiation (LTP) and dendritic spine density, two cellular phenomena thought to be involved in learning. Third, short-term calorie restriction, defined as a 30% reduction in caloric intake for two weeks, which naturally increases ghrelin levels and thus activates the receptor, was found to both increase both performance on spatial learning tasks as well as neurogenesis in the adult hippocampus.

Selective ligands

A range of selective ligands for the GHS-R receptor are now available and are being developed for several clinical applications. GHS-R agonists have appetite-stimulating and growth hormone-releasing effects, and are likely to be useful for the treatment of muscle wasting and frailty associated with old-age and degenerative diseases. On the other hand, GHS-R antagonists have anorectic effects and are likely to be useful for the treatment of obesity.

Agonists

• Adenosine
• Alexamorelin
• Anamorelin
• Capromorelin
• CP-464709
• Cortistatin-14
• Examorelin (hexarelin)
• Ghrelin (lenomorelin)
• GHRP-1
• GHRP-3
• GHRP-4
• GHRP-5
• GHRP-6
• Ibutamoren (MK-677)
• Ipamorelin
• L-692,585
• LY-426410
• LY-444711
• Macimorelin
• Pralmorelin (GHRP-2)
• Relamorelin
• SM-130,686
• Tabimorelin
• Ulimorelin

Antagonists

• A-778,193

Further reading

• Portelli J, Thielemans L, Ver Donck L, Loyens E, Coppens J, Aourz N, Aerssens J, Vermoesen K, Clinckers R, Schallier A, Michotte Y, Moechars D, Collingridge GL, Bortolotto ZA, Smolders I (July 2012). "Inactivation of the constitutively active ghrelin receptor attenuates limbic seizure activity in rodents". Neurotherapeutics. 9 (3): 658–72. doi:10.1007/s13311-012-0125-x. PMC 3441926 . PMID 22669710. 

External links

• "Ghrelin Receptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. 
• growth hormone secretagogue receptor at the US National Library of Medicine Medical Subject Headings (MeSH)
• Ghrelin at Colorado State University

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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• 1. グレリン ghrelin
• 2. ソマトスタチンの生理学とその類縁体 physiology of somatostatin and its analogues
• 3. 高齢者における衰弱：管理 failure to thrive in elderly adults management
• 4. 癌における食欲不振および悪液質の薬理学的マネージメント pharmacologic management of cancer anorexia cachexia
• 5. 成長ホルモンの生理学 physiology of growth hormone

English Journal

• Neutralizing circulating ghrelin by expressing a growth hormone secretagogue receptor-based protein protects against high-fat diet-induced obesity in mice.

• Gagnon J1,2, Zhu L3,4, Anini Y1,2, Wang Q3,4.
• Gene therapy.Gene Ther.2015 Sep;22(9):750-7. doi: 10.1038/gt.2015.38. Epub 2015 Jun 25.
• Ghrelin is a stomach-derived peptide hormone that stimulates appetite and promotes adiposity through binding to the growth hormone secretagogue receptor (GHS-R1a). Administration of ghrelin in rodents increases weight gain due to stimulating food intake and reducing fat utilization. Therefore, reduc
• PMID 25965396

• Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons.

• López Soto EJ1, Agosti F1, Cabral A1, Mustafa ER1, Damonte VM1, Gandini MA2, Rodríguez S1, Castrogiovanni D3, Felix R2, Perelló M1, Raingo J4.
• The Journal of general physiology.J Gen Physiol.2015 Sep;146(3):205-19. doi: 10.1085/jgp.201511383. Epub 2015 Aug 17.
• The growth hormone secretagogue receptor type 1a (GHSR1a) has the highest known constitutive activity of any G protein-coupled receptor (GPCR). GHSR1a mediates the action of the hormone ghrelin, and its activation increases transcriptional and electrical activity in hypothalamic neurons. Although GH
• PMID 26283199

• Ghrelin promotes renal cell carcinoma metastasis via Snail activation and is associated with poor prognosis.

• Lin TC1, Liu YP2, Chan YC1, Su CY1, Lin YF3, Hsu SL4, Yang CS5, Hsiao M1.
• The Journal of pathology.J Pathol.2015 Sep;237(1):50-61. doi: 10.1002/path.4552. Epub 2015 May 28.
• Ghrelin is an appetite-regulating molecule that promotes growth hormone (GH) release and food intake through growth hormone secretagogue receptor (GHS-R). Recently, high ghrelin levels have been detected in various types of human cancer. Ghrelin expression is observed in proximal and distal renal tu
• PMID 25925728

Japanese Journal

• グレリン受容体 : リガンド非依存性の恒常的活性化とその異常 (第5土曜特集 GPCR研究の最前線2016) -- (GPCR機能の新展開)

• 医学のあゆみ 256(5), 519-523, 2016-01-30
• NAID 40020717002

• Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

• Endocrine Journal 63(6), 555-561, 2016
• NAID 130005159557

• Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

• Endocrine Journal advpub(0), 2016
• NAID 130005143578

Related Links

• The growth hormone secretagogue receptor

The neuroendocrine hormone ghrelin, a recently discovered acylated peptide with numerous activities in various organ systems, exerts most of its known effects on the body through a highly conserved G-protein-coupled receptor, the growth hormone secretagogue receptor (GHSR) type 1a. The GHSR's wide expression in different tissues reflects activity ...

• Growth Hormone Secretagogue Receptor - an overview ...

Abstract. Growth hormone secretagogue receptor (GHSR) was originally identified as an orphan receptor in porcine and rat anterior pituitary membranes. In 1999, GHSR was deorphanized and shown to be a receptor for ghrelin, a peptide hormone secreted from the stomach. Therefore, GHSR is also called ghrelin receptor.

• The Ghrelin/Growth Hormone Secretagogue Receptor System ...

The Ghrelin/Growth Hormone Secretagogue Receptor System Is Involved in the Rapid and Sustained Antidepressant-Like Effect of Paeoniflorin The Ghrelin/Growth Hormone Secretagogue Receptor System Is Involved in the Rapid and Sustained Antidepressant-Like Effect of Paeoniflorin

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★リンクテーブル★

リンク元	「成長ホルモン分泌促進因子受容体」
関連記事	「grow」「growth」

「成長ホルモン分泌促進因子受容体」

　　[★]

英

growth hormone secretagogue receptor, GHS-R

「grow」

　　[★]

• v.

(過去: grew-過去分詞: grown)

• 成長する、生育する、伸びる

関

extend、growth、outgrow、outgrowth、stretch

　 　 　 　 　 　 　

「growth」

　　[★]

• n.

• 成長