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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 12 4908-4911
Copyright © 2000 by The Endocrine Society

Rapid Communications

Ghrelin Strongly Stimulates Growth Hormone Release in Humans

Kazuhiko Takaya, Hiroyuki Ariyasu, Naotetsu Kanamoto, Hiroshi Iwakura, Akihiro Yoshimoto, Masaki Harada, Kiyoshi Mori, Yasato Komatsu, Takeshi Usui, Akira Shimatsu, Yoshihiro Ogawa, Kiminori Hosoda, Takashi Akamizu, Masayasu Kojima, Kenji Kangawa and Kazuwa Nakao

Department of Medicine and Clinical Science (K.T., H.A., N.K., H.I., A.Y., M.H., K.M., Y.K., Y.O., K.H., T.A., K.N.), Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan; Clinical Research Institute Center for Endocrine and Metabolic Diseases (T.U., A.S.), Kyoto National Hospital, Kyoto 612-8555, Japan; and Department of Biochemistry, National Cardiovascular Center Research Institute (M.K., K.K.), Osaka 565-8565, Japan

Abstract

Ghrelin is a recently identified endogenous ligand for the GH secretagogue receptor and is involved in a novel system for regulating GH release. However, little is known about its GH-releasing activity and other endocrine effects in humans. To address this issue, we studied the GH, ACTH, cortisol, PRL, LH, FSH, and TSH responses to synthetic human ghrelin. In four normal male adults (28–37 yr), iv ghrelin administration released GH in a dose-dependent manner and 0.2, 1.0, and 5.0 µg/kg ghrelin produced 43.3 ± 6.0, 81.5 ± 12.7, and 107.0 ± 10.7 ng/mL of the GH peak values at 30 min, respectively. ACTH, cortisol, and PRL levels were also elevated after ghrelin injection, while the lowest dose (0.2 µg/kg) resulted in only minimum peak values of these hormones (22.8 ± 3.0 pg/mL, 9.4 ± 1.9 µg/dL, and 4.6 ± 0.6 ng/mL, respectively). There were no significant changes in LH, FSH, or TSH levels. This is the first study showing evidence that ghrelin strongly stimulates GH release in humans.




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 J. Clin. Endocrinol. Metab.Home page
U. Jaakkola, T. Kuusela, T. Jartti, U. Pesonen, M. Koulu, T. Vahlberg, and J. Kallio
The Leu7Pro Polymorphism of PreproNPY Is Associated with Decreased Insulin Secretion, Delayed Ghrelin Suppression, and Increased Cardiovascular Responsiveness to Norepinephrine during Oral Glucose Tolerance Test
J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3646 - 3652.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. M. Garcia, M. Garcia-Touza, R. A. Hijazi, G. Taffet, D. Epner, D. Mann, R. G. Smith, G. R. Cunningham, and M. Marcelli
Active Ghrelin Levels and Active to Total Ghrelin Ratio in Cancer-Induced Cachexia
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2920 - 2926.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. M. Avram, C. A. Jaffe, K. V. Symons, and A. L. Barkan
Endogenous Circulating Ghrelin Does Not Mediate Growth Hormone Rhythmicity or Response to Fasting
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2982 - 2987.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
Y. Nishi, H. Hiejima, H. Hosoda, H. Kaiya, K. Mori, Y. Fukue, T. Yanase, H. Nawata, K. Kangawa, and M. Kojima
Ingested Medium-Chain Fatty Acids Are Directly Utilized for the Acyl Modification of Ghrelin
Endocrinology, May 1, 2005; 146(5): 2255 - 2264.
[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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 Physiol. Rev.Home page
M. Kojima and K. Kangawa
Ghrelin: Structure and Function
Physiol Rev, April 1, 2005; 85(2): 495 - 522.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Stock, P. Leichner, A. C. K. Wong, M. A. Ghatei, T. J. Kieffer, S. R. Bloom, and J.-P. Chanoine
Ghrelin, Peptide YY, Glucose-Dependent Insulinotropic Polypeptide, and Hunger Responses to a Mixed Meal in Anorexic, Obese, and Control Female Adolescents
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2161 - 2168.
[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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 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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 J EndocrinolHome page
R. Guillemin
Hypothalamic hormones a.k.a. hypothalamic releasing factors
J. Endocrinol., January 1, 2005; 184(1): 11 - 28.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
H. Ariyasu, K. Takaya, H. Iwakura, H. Hosoda, T. Akamizu, Y. Arai, K. Kangawa, and K. Nakao
Transgenic Mice Overexpressing Des-Acyl Ghrelin Show Small Phenotype
Endocrinology, January 1, 2005; 146(1): 355 - 364.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
R. Barazzoni, A. Bosutti, M. Stebel, M. R. Cattin, E. Roder, L. Visintin, L. Cattin, G. Biolo, M. Zanetti, and G. Guarnieri
Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle
Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E228 - E235.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
N. Nagaya, J. Moriya, Y. Yasumura, M. Uematsu, F. Ono, W. Shimizu, K. Ueno, M. Kitakaze, K. Miyatake, and K. Kangawa
Effects of Ghrelin Administration on Left Ventricular Function, Exercise Capacity, and Muscle Wasting in Patients With Chronic Heart Failure
Circulation, December 14, 2004; 110(24): 3674 - 3679.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
G. N. Wade and J. E. Jones
Neuroendocrinology of nutritional infertility
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1277 - R1296.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. Ghizzoni, G. Mastorakos, A. Vottero, M. Ziveri, I. Ilias, and S. Bernasconi
Spontaneous Growth Hormone (GH) Secretion Is Not Directly Affected by Ghrelin in Either Short Normal Prepubertal Children or Children with GH Neurosecretory Dysfunction
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5488 - 5495.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. C. Ng, C. H. Lee, C. W. K. Lam, E. Wong, I. H. S. Chan, and T. F. Fok
Plasma Ghrelin and Resistin Concentrations Are Suppressed in Infants of Insulin-Dependent Diabetic Mothers
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5563 - 5568.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. R. Vulliemoz, E. Xiao, L. Xia-Zhang, M. Germond, J. Rivier, and M. Ferin
Decrease in Luteinizing Hormone Pulse Frequency during a Five-Hour Peripheral Ghrelin Infusion in the Ovariectomized Rhesus Monkey
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5718 - 5723.
[Abstract] [Full Text] [PDF]

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 Exp. Biol. Med.Home page
G. Rindi, A. Torsello, V. Locatelli, and E. Solcia
Ghrelin Expression and Actions: A Novel Peptide for an Old Cell Type of the Diffuse Endocrine System
Experimental Biology and Medicine, November 1, 2004; 229(10): 1007 - 1016.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
W. Zhang, T. R. Lin, Y. Hu, Y. Fan, L. Zhao, E. L. Stuenkel, and M. W. Mulholland
Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus
J. Physiol., September 15, 2004; 559(3): 729 - 737.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Helmling, C. Maasch, D. Eulberg, K. Buchner, W. Schroder, C. Lange, S. Vonhoff, B. Wlotzka, M. H. Tschop, S. Rosewicz, et al.
Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer
PNAS, September 7, 2004; 101(36): 13174 - 13179.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
M. S. Kim, C. Y. Yoon, P. G. Jang, Y. J. Park, C. S. Shin, H. S. Park, J. W. Ryu, Y. K. Pak, J. Y. Park, K. U. Lee, et al.
The Mitogenic and Antiapoptotic Actions of Ghrelin in 3T3-L1 Adipocytes
Mol. Endocrinol., September 1, 2004; 18(9): 2291 - 2301.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
N. Kanamoto, T. Akamizu, T. Tagami, Y. Hataya, K. Moriyama, K. Takaya, H. Hosoda, M. Kojima, K. Kangawa, and K. Nakao
Genomic Structure and Characterization of the 5'-Flanking Region of the Human Ghrelin Gene
Endocrinology, September 1, 2004; 145(9): 4144 - 4153.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. J. A. James, R. F. Drewett, and T. D. Cheetham
Low Cord Ghrelin Levels in Term Infants Are Associated with Slow Weight Gain Over the First 3 Months of Life
J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3847 - 3850.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
B. O. Yildiz, M. A. Suchard, M.-L. Wong, S. M. McCann, and J. Licinio
Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity
PNAS, July 13, 2004; 101(28): 10434 - 10439.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. M. Luque, R. D. Kineman, S. Park, X.-D. Peng, F. Gracia-Navarro, J. P. Castano, and M. M. Malagon
Homologous and Heterologous Regulation of Pituitary Receptors for Ghrelin and Growth Hormone-Releasing Hormone
Endocrinology, July 1, 2004; 145(7): 3182 - 3189.
[Abstract] [Full Text] [PDF]

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 J ANIM SCIHome page
B. E. Salfen, J. A. Carroll, D. H. Keisler, and T. A. Strauch
Effects of exogenous ghrelin on feed intake, weight gain, behavior, and endocrine responses in weanling pigs
J Anim Sci, July 1, 2004; 82(7): 1957 - 1966.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Endocr. Rev., June 1, 2004; 25(3): 426 - 457.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
R. K. Bains, S. E. Wells, D. M. Flavell, K. M. Fairhall, M. Strom, P. Le Tissier, and I. C. A. F. Robinson
Visceral Obesity without Insulin Resistance in Late-Onset Obesity Rats
Endocrinology, June 1, 2004; 145(6): 2666 - 2679.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Unniappan and R. E. Peter
In vitro and in vivo effects of ghrelin on luteinizing hormone and growth hormone release in goldfish
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1093 - R1101.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
W. Zhang, L. Zhao, T. R. Lin, B. Chai, Y. Fan, I. Gantz, and M. W. Mulholland
Inhibition of Adipogenesis by Ghrelin
Mol. Biol. Cell, May 1, 2004; 15(5): 2484 - 2491.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
A. INUI, A. ASAKAWA, C. Y. BOWERS, G. MANTOVANI, A. LAVIANO, M. M. MEGUID, and M. FUJIMIYA
Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ
FASEB J, March 1, 2004; 18(3): 439 - 456.
[Abstract] [Full Text] [PDF]

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 Exp. Biol. Med.Home page
R. R. Kraemer, R. J. Durand, E. O. Acevedo, L. G. Johnson, G. R. Kraemer, E. P. Hebert, and V. D. Castracane
Rigorous Running Increases Growth Hormone and Insulin-Like Growth Factor-I Without Altering Ghrelin
Experimental Biology and Medicine, March 1, 2004; 229(3): 240 - 246.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
P. Koutkia, G. Meininger, B. Canavan, J. Breu, and S. Grinspoon
Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy
Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E296 - E303.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
F. Gaytan, M. L. Barreiro, J. E. Caminos, L. K. Chopin, A. C. Herington, C. Morales, L. Pinilla, R. Paniagua, M. Nistal, F. F. Casanueva, et al.
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., January 1, 2004; 89(1): 400 - 409.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
S. R. Edmondson, S. P. Thumiger, G. A. Werther, and C. J. Wraight
Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems
Endocr. Rev., December 1, 2003; 24(6): 737 - 764.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. Q. Purnell, D. S. Weigle, P. Breen, and D. E. Cummings
Ghrelin Levels Correlate with Insulin Levels, Insulin Resistance, and High-Density Lipoprotein Cholesterol, But Not with Gender, Menopausal Status, or Cortisol Levels in Humans
J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5747 - 5752.
[Abstract] [Full Text] [PDF]

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 DiabetesHome page
G. Murdolo, P. Lucidi, C. Di Loreto, N. Parlanti, A. De Cicco, C. Fatone, C. G. Fanelli, G. B. Bolli, F. Santeusanio, and P. De Feo
Insulin is Required for Prandial Ghrelin Suppression in Humans
Diabetes, December 1, 2003; 52(12): 2923 - 2927.
[Abstract] [Full Text] [PDF]


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