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NEUROENDOCRINOLOGY

Ghrelin’s effects on growth hormone release: to pulse or not to pulse?

Nature Reviews Endocrinology volume 18, page 457 (2022)Cite this article

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Following the discovery in 1999 of ghrelin, the endogenous ligand for the growth hormone secretagogue (GHS) receptor (GHSR-1A)), there was much expectation that ghrelin would be found to have a role in the neuroendocrine regulatory network governing pulsatile GH secretion, with beneficial (GH-mediated) effects on bone and metabolism. Many studies had described the powerful effects of synthetic GHS (that is, ghrelin mimetics) in driving a GH response, including amplification of the response induced by GH-releasing hormone (GHRH).

Pulsatile GH secretion, which has a higher pulse amplitude in male than in female rodents, is driven by reciprocal control by GHRH neurons of the arcuate nucleus and somatostatin neurons of the periventricular nucleus, interacting both at the hypothalamic and pituitary level. That endogenous ghrelin might contribute to the GH secretory rhythm was first explored by the groups of Thérèse Bluet-Pagot and Jaques Epelbaum in 2005; in this important study they found that infusion of a GHSR-1A antagonist in male rats reduced GH pulse amplitude and the area under the curve, without affecting the pulsatile rhythm. The translational value of this work became apparent, as it was subsequently shown by Johannes Veldhuis and colleagues that 24 h ghrelin infusion to healthy humans amplified endogenous GH release, that is, pulse height and area under the curve, including that induced by GHRH.

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References

Original article

  • Zizzari, P. et al. Endogenous ghrelin regulates episodic growth hormone (GH) secretion by amplifying GH pulse amplitude: evidence from antagonism of the GH secretagogue-R1a receptor. Endocrinology 146, 3836–3842 (2005)

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  • Labarthe, A. et al. Effect of growth hormone secretagogue receptor deletion on growth, pulsatile growth hormone secretion, and meal pattern in male and female mice. Neuroendocrinology 112, 215–234 (2022)

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  • Hassouna, R. et al. An early reduction in GH peak amplitude in preproghrelin-deficient male mice has a minor impact on linear growth. Endocrinology 155, 3561–3571 (2014)

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  • Veldhuis, J. D. et al. Twenty-four hour continuous ghrelin infusion augments physiologically pulsatile, nycthemeral, and entropic (feedback-regulated) modes of growth hormone secretion. J. Clin. Endocrinol. Metab. 93, 3597–3603 (2008)

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Authors and Affiliations

  1. Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

    Suzanne L. Dickson

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  1. Suzanne L. Dickson
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Correspondence to Suzanne L. Dickson.

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Dickson, S.L. Ghrelin’s effects on growth hormone release: to pulse or not to pulse?. Nat Rev Endocrinol 18, 457 (2022). https://doi.org/10.1038/s41574-022-00698-z

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