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Known and Unknown Growth Hormone Secretagogue Receptors and their Ligands

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Book cover Ghrelin

Part of the book series: Endocrine Updates ((ENDO,volume 23))

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Abstract

The discovery of ghrelin is a typical example of reverse pharmacology: first the synthetic analogues (i.e. peptidyl and non-peptidyl growth hormone secretagogues (GHS)); second the receptor; third the natural ligand for this orphan receptor, i.e. ghrelin. Ghrelin is providing new understanding about how the gastrointestinal tract and nutritional intake regulate appetite, food intake and energy expenditure as well as the function of hypothalamus-pituitary axis, particularly the somatotroph function. However, ghrelin and its synthetic analogues also exert other peripheral, endocrine and nonendocrine actions including influence on the endocrine pancreas and glucose metabolism, on gastroenteropancreatic and cardiovascular functions, as well as modulation of cell proliferation. The classical ghrelin receptor, i.e., the GHS receptor type la (GHS-R1a) is widely distributed and mediates many of the biological actions of ghrelin and synthetic GHS. GHS-R type 1b a splice variant of the GHS-R1a, is even more widely distributed in central and peripheral tissues but its function is still unknown. Other GHS-R subtypes, i.e., other ghrelin receptors are likely to exist. In fact, GHS-R1a is bound by acylated ghrelin only but the existence of a receptor able to bind ghrelin independently of its acylation has been already demonstrated in agreement with evidence that unacylated ghrelin, although devoid of endocrine actions, possesses cardiovascular effects and modulates cell proliferation. Moreover, the existence of specific receptors mediating some cardiovascular actions of peptidyl GHS only and that do not recognize ghrelin has been demonstrated. Whether ghrelin is the sole ligand or one of a number of ligands activating the GHS-R1a is, at present, under investigation; on the other hand, it has also to be clarified whether the GHS-R used for ghrelin isolation is the sole receptor or one of a group of receptors for one or more than one ligand.

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Authors and Affiliations

  1. Department of Pharmacology, University of Turin Medical School, Turin, Italy

    Giampiero Muccioli, Fabio Broglio, Elena Tarabra & Ezio Ghigo

  2. Department of Internal Medicine, University of Turin Medical School, Turin, Italy

    Fabio Broglio & Ezio Ghigo

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  1. Giampiero Muccioli
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  2. Fabio Broglio
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  4. Ezio Ghigo
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Editors and Affiliations

  1. Division of Endocrinology and Metabolism Department of Internal Medicine, University of Turin, Italy

    Ezio Ghigo , Andrea Benso  & Fabio Broglio ,  & 

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Muccioli, G., Broglio, F., Tarabra, E., Ghigo, E. (2004). Known and Unknown Growth Hormone Secretagogue Receptors and their Ligands. In: Ghigo, E., Benso, A., Broglio, F. (eds) Ghrelin. Endocrine Updates, vol 23. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7971-0_3

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  • DOI: https://doi.org/10.1007/1-4020-7971-0_3

  • Publisher Name: Springer, Boston, MA

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