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Central Administration of Aminoprocalcitonin Inhibits Food Intake and Stimulates the Hypothalamic‐Pituitary‐Adrenal Axis in Rats via the Corticotrophin‐Releasing Factor System
Author(s) -
Tavares E.,
Maldonado R.,
GarciaMartinez A.,
Miñano F. J.
Publication year - 2012
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2012.02308.x
Subject(s) - medicine , endocrinology , hypothalamus , parvocellular cell , population , corticotropin releasing hormone , corticosterone , chemistry , biology , hormone , environmental health
Aminoprocalcitonin (N‐PCT), a neuroendocrine peptide derived from procalcitonin, reduces food intake and body weight when administered centrally in rats. We have recently shown that N‐PCT is expressed in brain areas known to be involved in energy homeostasis, including the paraventricular nucleus (PVN) of the hypothalamus, which contains a prominent population of corticotrophin‐releasing factor (CRF)‐synthesising neurones. CRF plays a pivotal role in the regulation of the hypothalamic‐pituitary adrenal (HPA) axis and food intake. However, little is known about functional interactions of N‐PCT and CRF. In the present study, we found endogenous N‐PCT protein in the rat PVN. We also showed N‐PCT immunoreactivity in PVN co‐localised with NeuN, a neuronal marker, or glial fibrillary acidic protein, an astrocyte marker. Double staining immunohistochemistry revealed that N‐PCT co‐localised with CRF in parvocellular neurones of the PVN. Intracerebroventricular N‐PCT administration increased CRF mRNA and content in the hypothalamus, suggesting that N‐PCT stimulates the HPA axis and suppresses food intake and body weight via CRF‐dependent pathways. In keeping with this, i.c.v. co‐injection of D‐Phe‐CRF 12‐41 , a CRF receptor antagonist, significantly attenuated N‐PCT‐induced reduction in food intake and body weight in a dose‐dependent manner. Furthermore, i.c.v. administration of N‐PCT increased plasma adrenocorticotrophic hormone and corticosterone concentrations and induced the expression of Fos protein, a marker of neuronal activity, in parvocellular CRF neurones. These data collectively support the hypothesis that N‐PCT inhibits food intake and body weight and stimulates the HPA axis via CRF‐mediated pathways.