Ghrelin indirectly activates hypophysiotropic CRF neurons in rodents

Agustina Cabral, Olga Suescun, Jeffrey M. Zigman, Mario Perello

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Ghrelin is a stomach-derived hormone that regulates food intake and neuroendocrine function by acting on its receptor, GHSR (Growth Hormone Secretagogue Receptor). Recent evidence indicates that a key function of ghrelin is to signal stress to the brain. It has been suggested that one of the potential stress-related ghrelin targets is the CRF (Corticotropin-Releasing Factor)-producing neurons of the hypothalamic paraventricular nucleus, which secrete the CRF neuropeptide into the median eminence and activate the hypothalamic-pituitary-adrenal axis. However, the neural circuits that mediate the ghrelin-induced activation of this neuroendocrine axis are mostly uncharacterized. In the current study, we characterized in vivo the mechanism by which ghrelin activates the hypophysiotropic CRF neurons in mice. We found that peripheral or intra-cerebro-ventricular administration of ghrelin strongly activates c-fos - a marker of cellular activation - in CRF-producing neurons. Also, ghrelin activates CRF gene expression in the paraventricular nucleus of the hypothalamus and the hypothalamic-pituitary-adrenal axis at peripheral level. Ghrelin administration directly into the paraventricular nucleus of the hypothalamus also induces c-fos within the CRF-producing neurons and the hypothalamic-pituitary-adrenal axis, without any significant effect on the food intake. Interestingly, dual-label immunohistochemical analysis and ghrelin binding studies failed to show GHSR expression in CRF neurons. Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons, albeit indirectly.

Original languageEnglish (US)
Article numbere31462
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 20 2012

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corticotropin-releasing hormone
ghrelin
Ghrelin
Corticotropin-Releasing Hormone
Neurons
Rodentia
rodents
neurons
paraventricular hypothalamic nucleus
Paraventricular Hypothalamic Nucleus
Ghrelin Receptor
Hypothalamus
food intake
Eating
Chemical activation
Median Eminence
neuropeptides
Neuropeptides
Gene expression
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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ghrelin indirectly activates hypophysiotropic CRF neurons in rodents. / Cabral, Agustina; Suescun, Olga; Zigman, Jeffrey M.; Perello, Mario.

In: PLoS One, Vol. 7, No. 2, e31462, 20.02.2012.

Research output: Contribution to journalArticle

Cabral, Agustina ; Suescun, Olga ; Zigman, Jeffrey M. ; Perello, Mario. / Ghrelin indirectly activates hypophysiotropic CRF neurons in rodents. In: PLoS One. 2012 ; Vol. 7, No. 2.
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