Articulo
Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus
Registro en:
issn:1873-3360
issn:0306-4530
Autor
Cabral, Agustina Soledad
Portiansky, Enrique Leo
Sánchez Jaramillo, Edith
Zigman, Jeffrey M.
Perelló, Mario Carlos
Institución
Resumen
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. Instituto Multidisciplinario de Biología Celular Laboratorio de Análisis de Imágenes