Cited by 41Regulation of Appetite and ObesityGrowth Hormone and Insulin-like Growth FactorsHypothalamic control of reproductive hormones

Ghrelin and obestatin modulate growth hormone-releasing hormone release and synaptic inputs onto growth hormone-releasing hormone neurons: Ghrelin and obestatin interactions in GHRH control

Feng, Dan D., Yang, Seung-Kwon, Loudes, Catherine, Simon, Axelle, Al-Sarraf, Tamara, Culler, Michael, Alvear-Perez, Rodrigo, Llorens-Cortes, Catherine +3 more·2011·European Journal of Neuroscience

Abstract

Ghrelin, a natural ligand of the growth hormone secretagogue receptor (GHS-R), is synthesized in the stomach but may also be expressed in lesser quantity in the hypothalamus where the GHS-R is located on growth hormone-releasing hormone (GHRH) neurons. Obestatin, a peptide derived from the same precursor as ghrelin, is able to antagonize the ghrelin-induced increase of growth hormone (GH) secretion in vivo but not from pituitary explants in vitro. Thus, the blockade of ghrelin-induced GH release by obestatin could be mediated at the hypothalamic level by the neuronal network that controls pituitary GH secretion. Ghrelin increased GHRH and decreased somatostatin (somatotropin-releasing inhibitory factor) release from hypothalamic explants, whereas obestatin only reduced the ghrelin-induced increase of GHRH release, thus indicating that the effect of ghrelin and obestatin is targeted to GHRH neurons. Patch-clamp recordings on mouse GHRH-enhanced green fluorescent protein neurons indicated that ghrelin and obestatin had no significant effects on glutamatergic synaptic transmission. Ghrelin decreased GABAergic synaptic transmission in 44% of the recorded neurons, an effect blocked in the presence of the GHS-R antagonist BIM28163, and stimulated the firing rate of 78% of GHRH neurons. Obestatin blocked the effects of ghrelin by acting on a receptor different from the GHS-R. These data suggest that: (i) ghrelin increases GHRH neuron excitability by increasing their action potential firing rate and decreasing the strength of GABA inhibitory inputs, thereby leading to an enhanced GHRH release; and (ii) obestatin counteracts ghrelin actions. Such interactions on GHRH neurons probably participate in the control of GH secretion.

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Crossref · 10.1111/j.1460-9568.2011.07787.x

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  • A large body of evidence supports the hypothesis that ghrelin acts on growth hormone secretion, at least in part, via stimulation of GHRH.

    “A large body of evidence supports the hypothesis that ghrelin acts on GH secretion, at least in part, via a stimulation of GHRH [39, 50, 192]”

    From Sleep and metabolic function (2012) · cites this paper as [50]

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Authors
Feng, D. D., Yang, S.-K., Loudes, C., Simon, A., Al-Sarraf, T., Culler, M., Alvear-Perez, R., Llorens-Cortes, C., Chen, C., Epelbaum, J., & Gardette, R.
Affiliations
  • Central South University (CN)
  • Inserm (FR)
  • Ipsen (United States) (US)
  • The University of Queensland (AU)
Corresponding author
Gardette, Robert
Venue
European Journal of Neuroscience
Publisher
Wiley
Published
2011-07-21
Volume
34
Issue
5
Pages
732-744
ISSN
0953-816X (ISSN-L)
OpenAlex
W1758501147
Cited by
41
References
84
Citations by year
2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 5 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 4
FWCI
2.07
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of California
  • Ipsen
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
ghrelin, obestatin, growth hormone secretagogue receptor, growth hormone secretion, GABAergic neurotransmission, neuronal excitability, somatostatin, hypothalamus, pituitary gland, glutamatergic neurotransmission
MeSH terms
Action Potentials, Animals, Bicuculline, Cricetulus, gamma-Aminobutyric Acid, Cricetinae, Male, Mice, Inbred C57BL, Synaptic Transmission, Neurons, Somatostatin, Growth Hormone-Releasing Hormone, Synapses, CHO Cells, Patch-Clamp Techniques, Glutamic Acid, Peptide Hormones, Mice, Ghrelin, Receptors, Ghrelin, GABA-A Receptor Antagonists

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