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Endocrinology Vol. 141, No. 11 4325-4328
Copyright © 2000 by The Endocrine Society

ARTICLES

The Novel Hypothalamic Peptide Ghrelin Stimulates Food Intake and Growth Hormone Secretion

A. M. Wren, C. J. Small, H. L. Ward, K. G. Murphy, C. L. Dakin, S. Taheri, A. R. Kennedy, G. H. Roberts, D. G. A. Morgan, M. A. Ghatei and S. R. Bloom

Address all correspondence and requests for reprints to: Stephen R. Bloom, M.D., Imperial College at Hammersmith Campus, Du Cane Road, 6th Floor Commonwealth Building, Division of Investigative Science, Hammersmith Hospital, London W12 ONN, United Kingdom.

Ghrelin, a novel 28 amino acid peptide found in hypothalamus and stomach, was recently identified as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). We have now found that both intracerebroventricular (ICV) and intraperitoneal (i.p.) administration of ghrelin in freely feeding rats stimulated food intake. The onset of increased feeding was rapid and after ICV administration was sustained for 24 hours. Following ICV administration of 3nmol ghrelin, the duration and magnitude of the feeding stimulation was similar to that following 5nmol neuropeptide Y (NPY). Plasma growth hormone (GH) concentration increased following both ICV and i.p. administration of ghrelin. Release of adrenocorticotrophic hormone (ACTH) was stimulated and thyroid stimulating hormone (TSH) inhibited following ICV administration of ghrelin. These data suggest a possible role for the newly identified endogenous hypothalamic peptide, ghrelin, in stimulation of feeding and growth hormone secretion.




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F. Levin, T. Edholm, P. T. Schmidt, P. Gryback, H. Jacobsson, M. Degerblad, C. Hoybye, J. J. Holst, J. F. Rehfeld, P. M. Hellstrom, et al.
Ghrelin Stimulates Gastric Emptying and Hunger in Normal-Weight Humans
J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3296 - 3302.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Szentirmai and J. M. Krueger
Central administration of neuropeptide Y induces wakefulness in rats
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R473 - R480.
[Abstract] [Full Text] [PDF]

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 J ANIM SCIHome page
M. E. Gordon and K. H. McKeever
Oral and intravenous carbohydrate challenges decrease active ghrelin concentrations and alter hormones related to control of energy metabolism in horses
J Anim Sci, July 1, 2006; 84(7): 1682 - 1690.
[Abstract] [Full Text] [PDF]

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 GutHome page
P Kobelt, S Helmling, A Stengel, B Wlotzka, V Andresen, B F Klapp, B Wiedenmann, S Klussmann, and H Monnikes
Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats
Gut, June 1, 2006; 55(6): 788 - 792.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. Li, X. Wu, Y. Zhao, S. Chen, and C. Owyang
Ghrelin acts on the dorsal vagal complex to stimulate pancreatic protein secretion
Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1350 - G1358.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. P. Kinzig, K. A. Scott, J. Hyun, S. Bi, and T. H. Moran
Lateral ventricular ghrelin and fourth ventricular ghrelin induce similar increases in food intake and patterns of hypothalamic gene expression
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2006; 290(6): R1565 - R1569.
[Abstract] [Full Text] [PDF]

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 Am. J. Clin. Nutr.Home page
G. Mingrone, L. Granato, E. Valera-Mora, A. Iaconelli, M. F Calvani, R. Bracaglia, M. Manco, G. Nanni, and M. Castagneto
Ultradian ghrelin pulsatility is disrupted in morbidly obese subjects after weight loss induced by malabsorptive bariatric surgery
Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1017 - 1024.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
L. P. Shearman, S.-P. Wang, S. Helmling, D. S. Stribling, P. Mazur, L. Ge, L. Wang, S. Klussmann, D. E. Macintyre, A. D. Howard, et al.
Ghrelin Neutralization by a Ribonucleic Acid-SPM Ameliorates Obesity in Diet-Induced Obese Mice
Endocrinology, March 1, 2006; 147(3): 1517 - 1526.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
K. J. Pulman, W. M. Fry, G. T. Cottrell, and A. V. Ferguson
The Subfornical Organ: A Central Target for Circulating Feeding Signals
J. Neurosci., February 15, 2006; 26(7): 2022 - 2030.
[Abstract] [Full Text] [PDF]

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 GutHome page
N M Neary, M R Druce, C J Small, and S R Bloom
Acylated ghrelin stimulates food intake in the fed and fasted states but desacylated ghrelin has no effect
Gut, January 1, 2006; 55(1): 135 - 135.
[Full Text] [PDF]

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 EndocrinologyHome page
J. Iqbal, Y. Kurose, B. Canny, and I. J. Clarke
Effects of Central Infusion of Ghrelin on Food Intake and Plasma Levels of Growth Hormone, Luteinizing Hormone, Prolactin, and Cortisol Secretion in Sheep
Endocrinology, January 1, 2006; 147(1): 510 - 519.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. I. Steinle, T. I. Pollin, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner
Variants in the Ghrelin Gene Are Associated with Metabolic Syndrome in the Old Order Amish
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6672 - 6677.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
M. Alba, D. Fintini, C. Y. Bowers, A. F. Parlow, and R. Salvatori
Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse
Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E762 - E767.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
S. Stanley, K. Wynne, B. McGowan, and S. Bloom
Hormonal Regulation of Food Intake
Physiol Rev, October 1, 2005; 85(4): 1131 - 1158.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
C.-C. Chang, C.-H. Hung, C.-S. Yen, K.-L. Hwang, and C.-Y. Lin
The relationship of plasma ghrelin level to energy regulation, feeding and left ventricular function in non-diabetic haemodialysis patients
Nephrol. Dial. Transplant., October 1, 2005; 20(10): 2172 - 2177.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
N Govoni, R De Iasio, C Cocco, A Parmeggiani, G Galeati, U Pagotto, C Brancia, M Spinaci, C Tamanini, R Pasquali, et al.
Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts
J. Endocrinol., September 1, 2005; 186(3): 505 - 513.
[Abstract] [Full Text] [PDF]

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 ChestHome page
N. Nagaya, T. Itoh, S. Murakami, H. Oya, M. Uematsu, K. Miyatake, and K. Kangawa
Treatment of Cachexia With Ghrelin in Patients With COPD
Chest, September 1, 2005; 128(3): 1187 - 1193.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. Zizzari, H. Halem, J. Taylor, J. Z. Dong, R. Datta, M. D. Culler, J. Epelbaum, and M. T. Bluet-Pajot
Endogenous Ghrelin Regulates Episodic Growth Hormone (GH) Secretion by Amplifying GH Pulse Amplitude: Evidence from Antagonism of the GH Secretagogue-R1a Receptor
Endocrinology, September 1, 2005; 146(9): 3836 - 3842.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
Y. Date, K. Toshinai, S. Koda, M. Miyazato, T. Shimbara, T. Tsuruta, A. Niijima, K. Kangawa, and M. Nakazato
Peripheral Interaction of Ghrelin with Cholecystokinin on Feeding Regulation
Endocrinology, August 1, 2005; 146(8): 3518 - 3525.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
M. Misra, K. K. Miller, K. Kuo, K. Griffin, V. Stewart, E. Hunter, D. B. Herzog, and A. Klibanski
Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents
Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E347 - E356.
[Abstract] [Full Text] [PDF]

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 Psychosom. Med.Home page
A. Masuda, M. Nakazato, T. Kihara, S. Minagoe, and C. Tei
Repeated Thermal Therapy Diminishes Appetite Loss and Subjective Complaints in Mildly Depressed Patients
Psychosom Med, July 1, 2005; 67(4): 643 - 647.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
L. F. Faulconbridge, H. J. Grill, and J. M. Kaplan
Distinct Forebrain and Caudal Brainstem Contributions to the Neuropeptide Y Mediation of Ghrelin Hyperphagia
Diabetes, July 1, 2005; 54(7): 1985 - 1993.
[Abstract] [Full Text] [PDF]

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 GutHome page
C Dornonville de la Cour, A Lindqvist, E Egecioglu, Y C L Tung, V Surve, C Ohlsson, J-O Jansson, C Erlanson-Albertsson, S L Dickson, and R Hakanson
Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice
Gut, July 1, 2005; 54(7): 907 - 913.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
B. Kola, E. Hubina, S. A. Tucci, T. C. Kirkham, E. A. Garcia, S. E. Mitchell, L. M. Williams, S. A. Hawley, D. G. Hardie, A. B. Grossman, et al.
Cannabinoids and Ghrelin Have Both Central and Peripheral Metabolic and Cardiac Effects via AMP-activated Protein Kinase
J. Biol. Chem., July 1, 2005; 280(26): 25196 - 25201.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
L. F. Canosa, S. Unniappan, and R. E. Peter
Periprandial changes in growth hormone release in goldfish: role of somatostatin, ghrelin, and gastrin-releasing peptide
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2005; 289(1): R125 - R133.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. Sato, Y. Fukue, H. Teranishi, Y. Yoshida, and M. Kojima
Molecular Forms of Hypothalamic Ghrelin and Its Regulation by Fasting and 2-Deoxy-D-Glucose Administration
Endocrinology, June 1, 2005; 146(6): 2510 - 2516.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
M. Groschl, H. G. Topf, J. Bohlender, J. Zenk, S. Klussmann, J. Dotsch, W. Rascher, and M. Rauh
Identification of Ghrelin in Human Saliva: Production by the Salivary Glands and Potential Role in Proliferation of Oral Keratinocytes
Clin. Chem., June 1, 2005; 51(6): 997 - 1006.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
E. Kellokoski, S. M. Poykko, A. H. Karjalainen, O. Ukkola, J. Heikkinen, Y. A. Kesaniemi, and S. Horkko
Estrogen Replacement Therapy Increases Plasma Ghrelin Levels
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2954 - 2963.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
J. Erdmann, F. Lippl, S. Wagenpfeil, and V. Schusdziarra
Differential Association of Basal and Postprandial Plasma Ghrelin With Leptin, Insulin, and Type 2 Diabetes
Diabetes, May 1, 2005; 54(5): 1371 - 1378.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
H. Iwakura, K. Hosoda, C. Son, J. Fujikura, T. Tomita, M. Noguchi, H. Ariyasu, K. Takaya, H. Masuzaki, Y. Ogawa, et al.
Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice
J. Biol. Chem., April 15, 2005; 280(15): 15247 - 15256.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
F. Gaytan, C. Morales, M. L. Barreiro, P. Jeffery, L. K. Chopin, A. C. Herington, F. F. Casanueva, E. Aguilar, C. Dieguez, and M. Tena-Sempere
Expression of Growth Hormone Secretagogue Receptor Type 1a, the Functional Ghrelin Receptor, in Human Ovarian Surface Epithelium, Mullerian Duct Derivatives, and Ovarian Tumors
J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1798 - 1804.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
W. Wei, G. Wang, X. Qi, E. W. Englander, and G. H. Greeley Jr.
Characterization and Regulation of the Rat and Human Ghrelin Promoters
Endocrinology, March 1, 2005; 146(3): 1611 - 1625.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Keen-Rhinehart and T. J. Bartness
Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R716 - R722.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
P. Kobelt, J. J. Tebbe, I. Tjandra, A. Stengel, H.-G. Bae, V. Andresen, I. R. van der Voort, R. W. Veh, C. R. Werner, B. F. Klapp, et al.
CCK inhibits the orexigenic effect of peripheral ghrelin
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R751 - R758.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
K. Wynne, S. Stanley, B. McGowan, and S. Bloom
Appetite control
J. Endocrinol., February 1, 2005; 184(2): 291 - 318.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
U. Espelund, T. K. Hansen, K. Hojlund, H. Beck-Nielsen, J. T. Clausen, B. S. Hansen, H. Orskov, J. O. L. Jorgensen, and J. Frystyk
Fasting Unmasks a Strong Inverse Association between Ghrelin and Cortisol in Serum: Studies in Obese and Normal-Weight Subjects
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 741 - 746.
[Abstract] [Full Text] [PDF]


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