Impact of the ghrelin signaling in the response of the hypothalamic?pituitary?adrenal axis to fasting

GUILLERMINA ZUBIRÍA; ANDRES GIOVAMBATTISTA; AGUSTINA CABRAL; ENRIQUE PORSTIANSKY; MARIO PERELLO; GIMENA FERNANDEZ; MIRTA REYNALDO

Congreso; II Congress of The Federation of Neuroscience Societies in Latin America, the Caribbean and the Iberian Peninsula; 2016

Ghrelin is a stomach-derived hormone that regulates food intake and several neuroendocrine functions. We had shown that the administration of ghrelin actives the hypothalamic?pituitary?adrenal (HPA) axis and corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN) via inhibition of the local γ-aminobutyric acid (GABA)ergic tone and independently of the arcuate nucleus (ARC). However, the impact of physiological increments of plasma ghrelin on CRF neurons and HPA axis is currently unknown. Here, we studied the response of the HPA axis, at hypothalamic and peripheral level, of 48-hour fasted wild-type or ghrelin receptor (GHSR)-null mice. In addition, we tested the GABA release from PVN explants of fed and fasted mice. We found that the lack of GHSR influences the peripheral response of the HPA axis as well as induction of the marker of cellular activation c-fos in the PVN CRF neurons. In contrast, GHSR expression is not necessary for fasting-induced increase of the neuropeptide Y-fiber density in the PVN. We also found a reduction of basal and high K-stimulated GABA release in PVN explants from fasted mice as compared to the release detected in explants from ad libitum fed mice. Thus, these data suggest that ghrelin signaling is relevant for the normal response of the HPA axis to fasting.