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Ghrelin: A History of Its Discovery

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Ghrelin in Health and Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 10))

Abstract

Historically, in 1981, growth hormone-releasing peptides (GHRPs) initially were thought to reflect the actions of elusive GHRH but fortunately in 1982 GHRH was isolated. By 1984 GHRP-6 results revealed that the actions of GHRH and GHRP were distinguishable from each other. To appreciate GHRP and GHRH interrelationships on GH release, detailed in vitro and in vivo dose–response studies were essential. Over subsequent years GHRPs were studied by many talented basic and clinical investigators. By 1995 GHRP icv administration was found to increase food intake in conscious rats and in 1996 the GHS-1a receptor was cloned. Finally, in 1999 the GHRP/GHS natural hormone, ghrelin, was isolated, synthesized, and found to have essentially the same activity as that of GHRPs/GHSs in animals and humans. A major surprise and a reorienting finding was the primary anatomical location of ghrelin in the stomach and, in addition, strong enhancement of food intake. Over time, GH secretion has been hypothesized to be primarily regulated by the hypothalamic hypophysiotropic tripartite system of GHRH, ghrelin, and SRIF rather than the bipartite system of GHRH and SRIF. Since the isolation of ghrelin, actions of this hormone have continued to expand from the hypothalamic CNS to peripheral sites. This includes both direct and indirect actions particularly related to nutrition and metabolism as well as a cornucopia of unexpected actions. In summary, unnatural GHRP begot natural ghrelin and its receptor. This reverse pharmacology approach forecasts that variations of the unnatural to natural sequence of events likely will be more frequent, modified, expanded, and refined in the future.

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Authors and Affiliations

  1. Department of Medicine, Endocrinology/Peptide Research, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL 53, New Orleans, LA, 70112, USA

    Cyril Y. Bowers M.D. & G. A. Reynolds B.A.

  2. Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA

    Johannes D. Veldhuis M.D.

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  1. Cyril Y. Bowers M.D.
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  2. G. A. Reynolds B.A.
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  3. Johannes D. Veldhuis M.D.
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Correspondence to Cyril Y. Bowers M.D. .

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  1. , Department of Metabolism and Aging, The Scripps Research Institute Florida, Scripps Way 3B3 130, Jupiter, 33458, Florida, USA

    Roy G. Smith

  2. , Department of Medicine, University of Virginia, Ray C Hunt Drive 450, Charlottesville, 22908, Virginia, USA

    Michael O. Thorner

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Bowers, C.Y., Reynolds, G.A., Veldhuis, J.D. (2012). Ghrelin: A History of Its Discovery. In: Smith, R., Thorner, M. (eds) Ghrelin in Health and Disease. Contemporary Endocrinology, vol 10. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-903-7_1

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