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

AGUSTINA CABRAL; GIMENA FERNANDEZ; GUILLERMINA ZUBIRIA; MIRTA REYNALDO; ANDRES GIOVAMBATTISTA; MARIO PERELLÓ

Congreso; 2nd FALAN Congress; 2016

Ghrelin is astomach-derived hormone that regulates food intake and several neuroendocrine functions. We had shown that theadministration of ghrelin actives the hypothalamic?pituitary?adrenal (HPA) axisand corticotropin-releasing factor (CRF) neurons of the hypothalamicparaventricular 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 HPAaxis 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)-nullmice. In addition, we tested the GABA release from PVN explants of fed andfasted mice.  We found that the lack of GHSRinfluences the peripheral response of the HPA axis as well as induction of themarker of cellular activation c-fos in the PVN CRFneurons. In contrast, GHSR expression is not necessary for fasting-induced increaseof the neuropeptide Y-fiber density in the PVN. We also found a reduction ofbasal and high K-stimulated GABA release in PVN explants from fasted mice ascompared to the release detected in explants from ad libitum fed mice. Thus, these data support the notion that ghrelin signaling is relevant for the normal response of the HPAaxis to fasting and these suggest that de NPY/GABA neurons engaged in thisresponse.