Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus

Agustina Cabral, Enrique Portiansky, Edith Sánchez-Jaramillo, Jeffrey M. Zigman, Mario Perello

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin's orexigenic action vs. its role as a stress signal are anatomically dissociated.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalPsychoneuroendocrinology
Volume67
DOIs
StatePublished - May 1 2016

Keywords

  • Ghrelin
  • Neuropeptide Y (NPY)
  • Orexigenic
  • Stress
  • γ-Aminobutyric acid (GABA)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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