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Ghrelin is a growth-hormone-releasing acylated peptide from stomach

Author

Listed:
  • Masayasu Kojima

    (National Cardiovascular Center Research Institute, Fujishirodai, Suita)

  • Hiroshi Hosoda

    (National Cardiovascular Center Research Institute, Fujishirodai, Suita)

  • Yukari Date

    (National Cardiovascular Center Research Institute, Fujishirodai, Suita)

  • Masamitsu Nakazato

    (Miyazaki Medical College)

  • Hisayuki Matsuo

    (National Cardiovascular Center Research Institute, Fujishirodai, Suita)

  • Kenji Kangawa

    (National Cardiovascular Center Research Institute, Fujishirodai, Suita)

Abstract

Small synthetic molecules called growth-hormone secretagogues (GHSs)1,2,3 stimulate the release of growth hormone (GH) from the pituitary4,5. They act through GHS-R, a G-protein-coupled receptor for which the ligand is unknown. Recent cloning of GHS-R6,7 strongly suggests that an endogenous ligand for the receptor does exist and that there is a mechanism for regulating GH release that is distinct from its regulation by hypothalamic growth-hormone-releasing hormone (GHRH)4,5. We now report the purification and identification in rat stomach of an endogenous ligand specific for GHS-R. The purified ligand is a peptide of 28 amino acids, in which the serine 3 residue is n-octanoylated. The acylated peptide specifically releases GH both in vivo and in vitro, and O-n-octanoylation at serine 3 is essential for the activity. We designate the GH-releasing peptide ‘ghrelin’ (ghre is the Proto-Indo-European root of the word ‘grow’). Human ghrelin is homologous to rat ghrelin apart from two amino acids. The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin.

Suggested Citation

  • Masayasu Kojima & Hiroshi Hosoda & Yukari Date & Masamitsu Nakazato & Hisayuki Matsuo & Kenji Kangawa, 1999. "Ghrelin is a growth-hormone-releasing acylated peptide from stomach," Nature, Nature, vol. 402(6762), pages 656-660, December.
    • Handle: RePEc:nat:nature:v:402:y:1999:i:6762:d:10.1038_45230
    DOI: 10.1038/45230
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    Cited by:

    1. Amany M Basuny & Moustafa A AboelAnin & Eman A Hamed, 2020. "Structure and Physiological Functions of Ghrelin," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 31(2), pages 24085-24092, October.
    2. Qian Wang, 2017. "The Ghrelin/GHS-R1a Pathway is Involved in the Mechanism of the CTA-regulated Neuronal Loop," International Journal of Sciences, Office ijSciences, vol. 6(01), pages 64-72, January.
    3. A. Lotfi & H. Aghdam-Shahryar & J. Ghiasi-Ghalehkandi & H. Kaiya & N. Maheri-Sis, 2011. "Effect of in ovo ghrelin administration on subsequent serum insulin and glucose levels in newly-hatched chicks," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 56(8), pages 377-380.
    4. Nazan Yurtcu & Canan Soyer Caliskan & Huri Guvey & Samettin Celik & Safak Hatirnaz & Andrea Tinelli, 2022. "Predictive and Diagnostic Value of Serum Adipokines in Pregnant Women with Intrahepatic Cholestasis," IJERPH, MDPI, vol. 19(4), pages 1-13, February.
    5. Mohammed Saeed Al-Ayed & Khaled Sadeq Al-Shaibari & Dhafer Alshehri & Mohammed Jamaan Alzahrani & Iman Nasser & Hamdan Saad Alaamri & Wed Ahmad Alaseeri & Ahmed A. Mahfouz & Saeed Ali Alsareii & Ahmed, 2020. "Serum Ghrelin Levels in Saudi Obese Asthmatic School-Children—Correlation with Interleukin-4, Interleukin-5, and Interleukin-21," IJERPH, MDPI, vol. 17(5), pages 1-11, March.
    6. Mahalaqua Nazli Khatib & Anuraj Shankar & Richard Kirubakaran & Kingsley Agho & Padam Simkhada & Shilpa Gaidhane & Deepak Saxena & Unnikrishnan B & Dilip Gode & Abhay Gaidhane & Syed Quazi Zahiruddin, 2015. "Effect of Ghrelin on Mortality and Cardiovascular Outcomes in Experimental Rat and Mice Models of Heart Failure: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-21, May.
    7. Enrica Bianchi & Kim Boekelheide & Mark Sigman & Susan J Hall & Kathleen Hwang, 2017. "Ghrelin modulates testicular damage in a cryptorchid mouse model," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-17, May.
    8. Gerrit Vortmeier & Stephanie H DeLuca & Sylvia Els-Heindl & Constance Chollet & Holger A Scheidt & Annette G Beck-Sickinger & Jens Meiler & Daniel Huster, 2015. "Integrating Solid-State NMR and Computational Modeling to Investigate the Structure and Dynamics of Membrane-Associated Ghrelin," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-28, March.
    9. K. Tanaka & T. Takizawa & O. Oki & K. Fukawa & T. Ito & M. Miyabe & H. Mannen & Y. Kurosawa & K. Hirose, 2015. "Allele frequency for c.335 A>C polymorphisms in porcine ghrelin/obestatin prepropeptide gene and association analysis with performance traits in various pig breeds," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 60(9), pages 411-416.
    10. Michelle L Johnson & M Jill Saffrey & Victoria J Taylor, 2016. "Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-12, November.

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