Ghrelin indirectly activates hypophysiotropic CRF neurons

AGUSTINA CABRAL; SPRING VALDIVIA; ANABELA PATRONE; MIRTA REYNALDO; OLGA SUESCUN; JEFFREY M. ZIGMAN; MARIO PERELLO

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Ghrelin is a stomach-derived hormone that acts on specific hypothalamic neurons and potently increases appetite. Also, ghrelin activates the CRF (Corticotropin-Releasing Factor)-producing neurons of the hypothalamic paraventricular nucleus (PVN) and, as a consequence, the neuroendocrine hypothalamic-pituitary-adrenal axis (HHA). However, the neural circuits mediating this activation are mostly uncharacterized. Here, we studied the circuits by which ghrelin activates the hypophysiotropic CRF neurons in vivo. We found that peripheral and central administration of ghrelin to wild type mice strongly activates the marker of cellular activation cfos in CRF-producing neurons. Also, ghrelin increase CRF mRNA expression in the PVN and the HHA axis at peripheral level. When directly administrated on the PVN, we found that ghrelin also activates the CRF-producing neurons and the HHA axis, without any significant effect on food intake. Unexpectedly, we found that CRF neurons do not express ghrelin receptor as indicated by in situ hybridization histochemistry and ghrelin binding studies. Thus, we conclude that ghrelin activates hypophysiotropic CRF neurons indirectly, likely via a local pre-synaptic mechanism.