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

CABRAL A; PORTIANSKY E; SÁNCHEZ-JARAMILLO E; ZIGMAN JM; PERELLO M

PSYCHONEUROENDOCRINOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 67 p. 27 - 39

0306-4530

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 -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 datasupport the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore,these data suggestthatthe neuronal circuits mediating ghrelin?s orexigenic action vs. its role as a stress signal are anatomically dissociated.