GHRL: Polycystic Ovarian Syndrome Database

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GHRL

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

GHRL

Aliases

MTLRP

Entrez Gene ID

51738

Gene Name

Ghrelin and obestatin prepropeptide

Chromosomal Location

3p25.3

HGNC ID

HGNC:18129

Summary

This gene encodes the ghrelin-obestatin preproprotein that is cleaved to yield two peptides, ghrelin and obestatin. Ghrelin is a powerful appetite stimulant and plays an important role in energy homeostasis. Its secretion is initiated when the stomach is empty, whereupon it binds to the growth hormone secretagogue receptor in the hypothalamus which results in the secretion of growth hormone (somatotropin). Ghrelin is thought to regulate multiple activities, including hunger, reward perception via the mesolimbic pathway, gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It was initially proposed that obestatin plays an opposing role to ghrelin by promoting satiety and thus decreasing food intake, but this action is still debated. Recent reports suggest multiple metabolic roles for obestatin, including regulating adipocyte function and glucose metabolism. Alternative splicing results in multiple transcript variants. In addition, antisense transcripts for this gene have been identified and may potentially regulate ghrelin-obestatin preproprotein expression. [provided by RefSeq, Nov 2014]

RefSeq DNA

NG_011560.1

RefSeq mRNA

NM_001134944.2, NR_126505.2, NM_016362.5, NM_001134941.3, NM_001134945.2, NM_001134946.2, NM_001302821.2, NM_001302822.2, NM_001302823.2, NM_001302824.2, NM_001302825.2

e!Ensembl

Gene	ENSG00000157017
Transcript	ENST00000335542, ENST00000430179, ENST00000422159, ENST00000449238, ENST00000437422, ENST00000287656, ENST00000457360, ENST00000439975, ENST00000446937, ENST00000429122, ENST00000425479
Protein	ENSP00000335074, ENSP00000399922, ENSP00000405464, ENSP00000388145, ENSP00000416768, ENSP00000287656, ENSP00000391406, ENSP00000403725, ENSP00000394923, ENSP00000414819, ENSP00000405031

Gene Ontology (GO)

Show/Hide all(46 )

GO ID	Ontology	Function	Evidence	Reference
GO:0000187	Biological process	Activation of MAPK activity	IMP	15350694
GO:0001696	Biological process	Gastric acid secretion	IBA	21873635
GO:0001937	Biological process	Negative regulation of endothelial cell proliferation	IDA	15572208
GO:0006006	Biological process	Glucose metabolic process	NAS	17392603
GO:0007186	Biological process	G protein-coupled receptor signaling pathway	ISS	10604470
GO:0007186	Biological process	G protein-coupled receptor signaling pathway	TAS	16511605
GO:0008154	Biological process	Actin polymerization or depolymerization	IDA	15232612
GO:0009725	Biological process	Response to hormone	IDA	15232612
GO:0009755	Biological process	Hormone-mediated signaling pathway	TAS	16511605
GO:0016358	Biological process	Dendrite development	IDA	16491079
GO:0016525	Biological process	Negative regulation of angiogenesis	NAS	15572208
GO:0030252	Biological process	Growth hormone secretion	TAS	16511605
GO:0032095	Biological process	Regulation of response to food	IBA	21873635
GO:0032691	Biological process	Negative regulation of interleukin-1 beta production	IDA	15232612
GO:0040018	Biological process	Positive regulation of multicellular organism growth	IC	16511605
GO:0042127	Biological process	Regulation of cell proliferation	IDA	15564328, 16394173
GO:0042322	Biological process	Negative regulation of circadian sleep/wake cycle, REM sleep	IDA	18329818
GO:0042536	Biological process	Negative regulation of tumor necrosis factor biosynthetic process	IDA	15232612
GO:0043066	Biological process	Negative regulation of apoptotic process	IDA	15158140
GO:0043400	Biological process	Cortisol secretion	NAS	17201814
GO:0043627	Biological process	Response to estrogen	IDA	15292338
GO:0045409	Biological process	Negative regulation of interleukin-6 biosynthetic process	IDA	15232612
GO:0046010	Biological process	Positive regulation of circadian sleep/wake cycle, non-REM sleep	IDA	18329818
GO:0046697	Biological process	Decidualization	IDA	17494105
GO:0050728	Biological process	Negative regulation of inflammatory response	IBA	21873635
GO:0050728	Biological process	Negative regulation of inflammatory response	IDA	15232612
GO:0051216	Biological process	Cartilage development	NAS	15576457
GO:0051461	Biological process	Positive regulation of corticotropin secretion	IDA	12566947
GO:0051464	Biological process	Positive regulation of cortisol secretion	IDA	12566947, 18329818
GO:0051965	Biological process	Positive regulation of synapse assembly	IDA	16491079
GO:0060124	Biological process	Positive regulation of growth hormone secretion	IBA	21873635
GO:0060124	Biological process	Positive regulation of growth hormone secretion	IDA	12566947, 18329818
GO:0060399	Biological process	Positive regulation of growth hormone receptor signaling pathway	IC	12566947
GO:0120162	Biological process	Positive regulation of cold-induced thermogenesis	ISS	19666521
GO:0005576	Cellular component	Extracellular region	IDA	17392603
GO:0005615	Cellular component	Extracellular space	IBA	21873635
GO:0005615	Cellular component	Extracellular space	IDA	15039149, 15531532
GO:0030424	Cellular component	Axon	IDA	17113048
GO:0001664	Molecular function	G protein-coupled receptor binding	ISS	10604470
GO:0005515	Molecular function	Protein binding	IPI	25416956
GO:0016608	Molecular function	Growth hormone-releasing hormone activity	IBA	21873635
GO:0016608	Molecular function	Growth hormone-releasing hormone activity	ISS	10604470
GO:0016608	Molecular function	Growth hormone-releasing hormone activity	TAS	16511605
GO:0030296	Molecular function	Protein tyrosine kinase activator activity	IMP	15350694
GO:0031768	Molecular function	Ghrelin receptor binding	IBA	21873635
GO:0031768	Molecular function	Ghrelin receptor binding	TAS	16511605

Protein Information

Protein Name

Appetite-regulating hormone, In2c-preproghrelin, ghrelin, growth hormone secretagogue receptor ligand, ghrelin/obestatin preprohormone, ghrelin/obestatin prepropeptide, growth hormone-releasing peptide, motilin-related peptide, prepro-appetite regulatory hormone, preproghrelin

Function

Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation.; Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility

Refseq Proteins

NP_001128416.1, , NP_057446.1, NP_001128413.1, NP_001128417.1, NP_001128418.1, NP_001289750.1, NP_001289751.1, NP_001289752.1, NP_001289753.1, NP_001289754.1

UniProt

Q9UBU3

PDB

1P7X

Pathways
	KEGG	Reactome
	cAMP signaling pathway Neuroactive ligand-receptor interaction	G alpha (q) signalling events Synthesis, secretion, and deacylation of Ghrelin

Interactions

STRING	MINT	IntAct
ENSP00000375844		Q9HC96

View interactions

Associated Diseases

Show/Hide all(8 )

Disease group	Disease Name	References
Cardiovascular Diseases
	Heart Failure	20572026
	Myocardial Failure	20572026
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
	Diastematomyelia	17400914
	Anencephaly	17400914
	Atonic seizures	19429016
	Neurenteric Cyst	17400914
	Primary tethered cord syndrome	17400914
	Status Dysraphicus	17400914
Digestive System Diseases
	Gastric ulcer	15177919, 16259727
	Colitis	19617644
Endocrine System Diseases
Endocrine System Diseases	PCOS	17276431
Neoplasms
	Adenocarcinoma	21472143
	Carcinoma	21472143
	Esophagus Neoplasm	21472143
	Cribriform Carcinoma	21472143
Nervous System Diseases
	Seizures	19429016
	Neural Tube Defects	17400914
	Jacksonian Seizure	19429016
Nutritional and Metabolic Diseases
Nutritional and Metabolic Diseases	Obesity	11502844, 12050239, 16204371
Psychiatric/Brain disorders
	Mental Depression	19272368
	Schizophrenia	22369141
	Melancholia	19272368
	Eating Disorders	30677719

References

Show/Hide all(23)

PubMed ID	Associated gene/s	Associated condition	Genetic Mutation	Diagnostic Criteria	Association with PCOS	Ethnicity	Conclusion
17276431	GH,Glucose and Insulin			Rotterdam criteria	Related	20 PCOS and 15control	Injection of ghrelin seems to override the GH secretion defect in obese women with PCOS
18362298		Obesity			Related	UK British/Irish origin-50 PCOS,28 controls and 22 body mass index (BMI)/fat mass-matched pairs	In women with PCOS, serum ghrelin levels are suppressed, showing a negative relationship with HOMA2 IR and a blunted response to oral glucose.
18756827	Leptin				Related	45 PCOS and 20 controls	ghrelin level in women with PCOS reflects the metabolic and hormonal changes
18812636	PYY,serum adiponectin,sCD40L,visfatin, sP-, sE-selectins, resistin	Pancreatic islet adaptation to insulin resistance,low-grade chronic inflammation,endothelial dysfunction,atherosclerosis,obesity		Rotterdam criteria	Related		The study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles
18812636		chronic inflammation		Rotterdam criteria	Related	40 PCOS and 20controls	The study confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.
18937712	Leptin and Resistin				Related	16 obesePCOS,12 lean PCOS and 19 Control	ghrelin and E2 for the elevated LH/FSH ratio and resistin for the lowered SHBG
19031219					Related	45 women with PCOS and 20 controls	ghrelin level in women with PCOS reflects the metabolic and hormonal changes which are characteristics of the syndrome
23158749	Adiponectin and leptin	Obesity			Related	17 PCOS and 21 Control	ghrelin presents no significant correlation
21458334	Homocysteine				Related	44 PCOS and 20 Control	ghrelin levels were depressed with polycystic ovary syndrome in relation to obesity
21216086					Direct	Saudi (30 PCOS and 30 Control)	No relationship between circulating ghrelin levels and the abnormal hormonal pattern of the PCOS
20537572					Related	13 obese PCOS , 13 lean PCOS , 10 obese control and 10 lean control	Low ghrelin levels in obese PCOS patients
19049992				Rotterdam criteria	Direct	Chinese (271 PCOS and 296 control)	no association with PCOS
18250617					Related	9 PCOS, 6 obese controls, and 6Control	In both obese and PCOS obese patients, leptin levels are not influenced by ghrelin administration
18075283	Insulin				Direct	8 PCOS and 8 Control	no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS
18065576	cholecystokinin,Insulin and Peptide YY				Related	14 PCOS and 14 Control	PCOS was associated with lower fasting ghrelin and a smaller postprandial ghrelin suppression both before and after weight loss
17616856	Adiponectin				Related	20 PCOS,45 healthy lean and 37 obese	ghrelin levels in PCOS women were significantly higher than in obese women
17163351					Related		ghrelin expression plays an important role in the direct control of ovarian development and function.
16868149	Adiponectin				Related	51PCOS and 63 controls	ghrelin levels were decreased in hirsute PCOS patients
15942248	Adiponectin				Related	36 PCOS	Both adiponectin and ghrelin can be involved in the pathophysiology of PCOS
15890737		Hyperandrogenism		Rotterdam criteria	Related	259 PCOS, 25 hyperandrogenaemia and 46 controls	In PCOS circulating ghrelin and androgens are inversely related and it is possible that this peptide is involved in steroidal synthesis
15240612				NIH criteria	Related	10 PCOS and 6 control	As measured by subjective short-term hunger and satiety and ghrelin homeostasis, may be impaired in PCOS.
15057670					Related	52 PCOS and 16Control	ghrelin could be the possible link in PCOS etiology
12574237					Direct	33 PCOS and 32control	no relationship between circulating ghrelin and the abnormal hormonal pattern of the PCOS syndrome