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DOI: 10.1055/s-0029-1233462
© Georg Thieme Verlag KG Stuttgart · New York
Expression of Ghrelin and its Receptor in Human Tissues
Publication History
received 20.03.2008
accepted 22.06.2009
Publication Date:
10 August 2009 (online)

Abstract
Ghrelin is a peptide thought to be involved in the regulation of appetite. Furthermore, significant effects on the release of growth hormone (GH) and ACTH were demonstrated. Contributing to the physiological relevance of this hormone, we investigated the expression of ghrelin and its receptor (GHS-R) in several normal human tissues. RNA samples (BD Biosciences) underwent one-step TaqMan Real-Time RT-PCR. Immunohistochemistry was performed on paraffin-embedded tissues using specific primary antibodies against ghrelin and its receptor. Relevant ghrelin mRNA levels were detected in all human tissues with the highest levels in stomach, pituitary, and small intestine. By immunohistochemistry, ghrelin peptide expression was detectable in reproductive and endocrine organs (ovary, anterior pituitary, adrenal gland), and organs of the gastrointestinal tract (stomach, pancreas). GHS-R1a mRNA expression was demonstrated in 10 of 24 human organs analyzed with the highest levels in pituitary, adrenal gland, and spinal cord. Expression of the receptor peptide was detected by immunohistochemistry in endocrine and reproductive organs (anterior pituitary, thyroid, pancreas, testis), parts of the CNS (cerebrum, cerebellum), and in single cells of bone marrow. Expression of both ghrelin and its receptor in endocrine and reproductive organs may indicate new endocrine or paracrine mechanisms of regulation in these tissues.
Key words
GHS-R1a - mRNA - protein - human
References
- 1
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K.
Ghrelin is a growth-hormone-releasing acylated peptide from stomach.
Nature.
1999;
402
656-660
MissingFormLabel
- 2
Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M.
Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct
endocrine cell type in the gastrointestinal tracts of rats and humans.
Endocrinology.
2000;
141
4255-4261
MissingFormLabel
- 3
Date Y, Nakazato M, Hashiguchi S, Dezaki K, Mondal MS, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S.
Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin
secretion.
Diabetes.
2002;
51
124-129
MissingFormLabel
- 4
Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M.
The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R,
in humans.
J Clin Endocrinol Metab.
2002;
87
2988
MissingFormLabel
- 5
Gualillo O, Caminos J, Blanco M, Garcia-Caballero T, Kojima M, Kangawa K, Dieguez C, Casanueva F.
Ghrelin, a novel placental-derived hormone.
Endocrinology.
2001;
142
788-794
MissingFormLabel
- 6
Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, Inagaki C.
GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells,
B cells, and neutrophils.
J Clin Endocrinol Metab.
2001;
86
4284-4291
MissingFormLabel
- 7
Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH.
A receptor in pituitary and hypothalamus that functions in growth hormone release.
Science.
1996;
273
974-977
MissingFormLabel
- 8
Korbonits M, Kojima M, Kangawa K, Grossman AB.
Presence of ghrelin in normal and adenomatous human pituitary.
Endocrine.
2001;
14
101-104
MissingFormLabel
- 9
Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K.
Kidney produces a novel acylated peptide, ghrelin.
FEBS Lett.
2000;
486
213-216
MissingFormLabel
- 10
Tena-Sempere M, Barreiro ML, Gonzalez LC, Gaytan F, Zhang FP, Caminos JE, Pinilla L, Casanueva FF, Dieguez C, Aguilar E.
Novel expression and functional role of ghrelin in rat testis.
Endocrinology.
2002;
143
717-725
MissingFormLabel
- 11
Arvat E, Maccario M, Di Vito L, Broglio F, Benso A, Gottero C, Papotti M, Muccioli G, Dieguez C, Casanueva FF, Deghenghi R, Camanni F, Ghigo E.
Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans:
comparison and interactions with hexarelin, a non-natural peptidyl GHS, and GH-releasing
hormone.
J Clin Endocrinol Metab.
2001;
86
1169-1174
MissingFormLabel
- 12
Cunha SR, Mayo KE.
Ghrelin and growth hormone (GH) secretagogues potentiate GH-releasing hormone (GHRH)-induced
cyclic adenosine 3′,5′-monophosphate production in cells expressing transfected GHRH
and GH secretagogue receptors.
Endocrinology.
2002;
143
4570-4582
MissingFormLabel
- 13
Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K.
Ghrelin strongly stimulates growth hormone release in humans.
J Clin Endocrinol Metab.
2000;
85
4908-4911
MissingFormLabel
- 14
Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E.
Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia
and reduces insulin secretion in humans.
J Clin Endocrinol Metab.
2001;
86
5083-5086
MissingFormLabel
- 15
Lee HM, Wang G, Englander EW, Kojima M, Greeley Jr GH.
Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion:
enteric distribution, ontogeny, influence of endocrine, and dietary manipulations.
Endocrinology.
2002;
143
185-190
MissingFormLabel
- 16
Murata M, Okimura Y, Iida K, Matsumoto M, Sowa H, Kaji H, Kojima M, Kangawa K, Chihara K.
Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells.
J Biol Chem.
2002;
277
5667-5674
MissingFormLabel
- 17
Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K.
Hemodynamic and hormonal effects of human ghrelin in healthy volunteers.
Am J Physiol Regul Integr Comp Physiol.
2001;
280
R1483-R1487
MissingFormLabel
- 18
Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR.
Ghrelin enhances appetite and increases food intake in humans.
J Clin Endocrinol Metab.
2001;
86
5992
MissingFormLabel
- 19
Muccioli G, Baragli A, Granata R, Papotti M, Ghigo E.
Heterogeneity of ghrelin/growth hormone secretagogue receptors.
Toward the understanding of the molecular identity of novel ghrelin/GHS receptors.
Neuroendocrinology.
2007;
86
147-164
MissingFormLabel
- 20
McKee KK, Palyha OC, Feighner SD, Hreniuk DL, Tan CP, Phillips MS, Smith RG, Van der Ploeg LH, Howard AD.
Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors.
Mol Endocrinol.
1997;
11
415-423
MissingFormLabel
- 21
Yokote R, Sato M, Matsubara S, Ohye H, Niimi M, Murao K, Takahara J.
Molecular cloning and gene expression of growth hormone-releasing peptide receptor
in rat tissues.
Peptides.
1998;
19
15-20
MissingFormLabel
- 22
Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD.
Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and
peripheral tissues.
Brain Res Mol Brain Res.
1997;
48
23-29
MissingFormLabel
- 23
Jeffery PL, Herington AC, Chopin LK.
Expression and action of the growth hormone releasing peptide ghrelin and its receptor
in prostate cancer cell lines.
J Endocrinol.
2002;
172
R7-R11
MissingFormLabel
- 24
Sun Y, Wang P, Zheng H, Smith RG.
Ghrelin stimulation of growth hormone release and appetite is mediated through the
growth hormone secretagogue receptor.
Proc Natl Acad Sci USA.
2004;
101
4679-4684
MissingFormLabel
- 25
Papotti M, Cassoni P, Volante M, Deghenghi R, Muccioli G, Ghigo E.
Ghrelin-producing endocrine tumors of the stomach and intestine.
J Clin Endocrinol Metab.
2001;
86
5052-5059
MissingFormLabel
- 26
Papotti M, Ghe C, Cassoni P, Catapano F, Deghenghi R, Ghigo E, Muccioli G.
Growth hormone secretagogue binding sites in peripheral human tissues.
J Clin Endocrinol Metab.
2000;
85
3803-3807
MissingFormLabel
- 27
Ueberberg B, Unger N, Sheu SY, Walz MK, Schmid KW, Saeger W, Mann K, Petersenn S.
Differential expression of ghrelin and its receptor (GHS-R1a) in various adrenal tumors
and normal adrenal gland.
Horm Metab Res.
2008;
40
181-188
MissingFormLabel
- 28
Carraro G, Albertin G, Abudukerimu A, Aragona F, Nussdorfer GG.
Growth hormone secretagogue receptor subtypes 1a and 1b are expressed in the human
adrenal cortex.
Int J Mol Med.
2004;
13
295-298
MissingFormLabel
- 29
Tortorella C, Macchi C, Spinazzi R, Malendowicz LK, Trejter M, Nussdorfer GG.
Ghrelin, an endogenous ligand for the growth hormone-secretagogue receptor, is expressed
in the human adrenal cortex.
Int J Mol Med.
2003;
12
213-217
MissingFormLabel
- 30
Volante M, Allia E, Gugliotta P, Funaro A, Broglio F, Deghenghi R, Muccioli G, Ghigo E, Papotti M.
Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells
and related endocrine tumors.
J Clin Endocrinol Metab.
2002;
87
1300-1308
MissingFormLabel
- 31
Korbonits M, Bustin SA, Kojima M, Jordan S, Adams EF, Lowe DG, Kangawa K, Grossman AB.
The expression of the growth hormone secretagogue receptor ligand ghrelin in normal
and abnormal human pituitary and other neuroendocrine tumors.
J Clin Endocrinol Metab.
2001;
86
881-887
MissingFormLabel
- 32
Kamegai J, Tamura H, Shimizu T, Ishii S, Tatsuguchi A, Sugihara H, Oikawa S, Kineman RD.
The role of pituitary ghrelin in growth hormone (GH) secretion: GH-releasing hormone-dependent
regulation of pituitary ghrelin gene expression and peptide content.
Endocrinology.
2004;
145
3731-3738
MissingFormLabel
- 33
Kineman RD, Kamegai J, Frohman LA.
Growth hormone (GH)-releasing hormone (GHRH) and the GH secretagogue (GHS), L692,585,
differentially modulate rat pituitary GHS receptor and GHRH receptor messenger ribonucleic
acid levels.
Endocrinology.
1999;
140
3581-3586
MissingFormLabel
- 34
Kanamoto N, Akamizu T, Hosoda H, Hataya Y, Ariyasu H, Takaya K, Hosoda K, Saijo M, Moriyama K, Shimatsu A, Kojima M, Kangawa K, Nakao K.
Substantial production of ghrelin by a human medullary thyroid carcinoma cell line.
J Clin Endocrinol Metab.
2001;
86
4984-4990
MissingFormLabel
- 35
Raghay K, Garcia-Caballero T, Nogueiras R, Morel G, Beiras A, Dieguez C, Gallego R.
Ghrelin localization in rat and human thyroid and parathyroid glands and tumours.
Histochem Cell Biol.
2006;
125
239-246
MissingFormLabel
- 36
Volante M, Allia E, Fulcheri E, Cassoni P, Ghigo E, Muccioli G, Papotti M.
Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects
on tumor growth.
Am J Pathol.
2003;
162
645-654
MissingFormLabel
- 37
Gaytan F, Barreiro ML, Chopin LK, Herington AC, Morales C, Pinilla L, Casanueva FF, Aguilar E, Dieguez C, Tena-Sempere M.
Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone
secretagogue receptor, in the cyclic human ovary.
J Clin Endocrinol Metab.
2003;
88
879-887
MissingFormLabel
- 38
Gaytan F, Barreiro ML, Caminos JE, Chopin LK, Herington AC, Morales C, Pinilla L, Paniagua R, Nistal M, Casanueva FF, Aguilar E, Dieguez C, Tena-Sempere M.
Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue
receptor, in normal human testis and testicular tumors.
J Clin Endocrinol Metab.
2004;
89
400-409
MissingFormLabel
- 39
Bennett PA, Thomas GB, Howard AD, Feighner SD, van der Ploeg LH, Smith RG, Robinson IC.
Hypothalamic growth hormone secretagogue-receptor (GHS-R) expression is regulated
by growth hormone in the rat.
Endocrinology.
1997;
138
4552-4557
MissingFormLabel
- 40
Katayama M, Nogami H, Nishiyama J, Kawase T, Kawamura K.
Developmentally and regionally regulated expression of growth hormone secretagogue
receptor mRNA in rat brain and pituitary gland.
Neuroendocrinology.
2000;
72
333-340
MissingFormLabel
- 41
Kim MS, Yoon CY, Park KH, Shin CS, Park KS, Kim SY, Cho BY, Lee HK.
Changes in ghrelin and ghrelin receptor expression according to feeding status.
Neuroreport.
2003;
14
1317-1320
MissingFormLabel
- 42
Kojima M, Hosoda H, Kangawa K.
Purification and distribution of ghrelin: the natural endogenous ligand for the growth
hormone secretagogue receptor.
Horm Res.
2001;
56
((Suppl 1))
93-97
MissingFormLabel
- 43
Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S.
A role for ghrelin in the central regulation of feeding.
Nature.
2001;
409
194-198
MissingFormLabel
- 44
Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, Hayashi T, Inoue G, Hosoda K, Kojima M, Kangawa K, Nakao K.
Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide
that antagonizes leptin action through the activation of hypothalamic neuropeptide
Y/Y1 receptor pathway.
Diabetes.
2001;
50
227-232
MissingFormLabel
- 45
Tschop M, Smiley DL, Heiman ML.
Ghrelin induces adiposity in rodents.
Nature.
2000;
407
908-913
MissingFormLabel
- 46
Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR.
The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion.
Endocrinology.
2000;
141
4325-4328
MissingFormLabel
- 47
Volante M, Fulcheri E, Allia E, Cerrato M, Pucci A, Papotti M.
Ghrelin expression in fetal, infant, and adult human lung.
J Histochem Cytochem.
2002;
50
1013-1021
MissingFormLabel
- 48
Yabuki A, Taharaguchi S, Ichii O, Kojima M, Nishi Y, Mifune H, Kamimura R, Matsumoto M, Suzuki S.
Immunohistochemical localization of ghrelin in rodent kidneys.
Histochem Cell Biol.
2006;
126
231-238
MissingFormLabel
- 49
Guebre-Egziabher F, Bernhard J, Geelen G, Malvoisin E, Hadj-Aissa A, Fouque D.
Leptin, adiponectin, and ghrelin dysregulation in chronic kidney disease.
J Ren Nutr.
2005;
15
116-120
MissingFormLabel
- 50
Iglesias MJ, Pineiro R, Blanco M, Gallego R, Dieguez C, Gualillo O, Gonzalez-Juanatey JR, Lago F.
Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes.
Cardiovasc Res.
2004;
62
481-488
MissingFormLabel
- 51
Enomoto M, Nagaya N, Uematsu M, Okumura H, Nakagawa E, Ono F, Hosoda H, Oya H, Kojima M, Kanmatsuse K, Kangawa K.
Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel
growth hormone-releasing peptide, in healthy humans.
Clin Sci (Lond).
2003;
105
431-435
MissingFormLabel
- 52
Frascarelli S, Ghelardoni S, Ronca-Testoni S, Zucchi R.
Effect of ghrelin and synthetic growth hormone secretagogues in normal and ischemic
rat heart.
Basic Res Cardiol.
2003;
98
401-405
MissingFormLabel
- 53
Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W, Ueno K, Kitakaze M, Miyatake K, Kangawa K.
Effects of ghrelin administration on left ventricular function, exercise capacity,
and muscle wasting in patients with chronic heart failure.
Circulation.
2004;
110
3674-3679
MissingFormLabel
Correspondence
Prof. Dr. med. S. Petersenn
Department of Endocrinology and Division of Laboratory Research
University of Duisburg-Essen
Hufelandstr. 55
45122 Essen
Phone: +49 201 723 2854
Fax: +49 201 723 5976
Email: stephan.petersenn@uni-due.de