title: Central administration of aminoprocalcitonin inhibits food intake and stimulates the hypothalamic-pituitary-adrenal axis in rats via the corticotrophin-releasing factor system.
abstract: 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.
authors.affiliation: Unidad de Farmacología Experimental y Clínica (UFEC), Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Tavares
authors.forename: R
authors.initials: R
authors.lastname: Maldonado
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Martinez
authors.forename: F J
authors.initials: FJ
authors.lastname: Miñano
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002116:Calcitonin / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D002490:Central Nervous System / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011498:Protein Precursors / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013268:Stimulation, Chemical
chemical_list: C000606591:Calca protein, rat; D011498:Protein Precursors; D002116:Calcitonin; D003346:Corticotropin-Releasing Hormone; D015740:Calcitonin Gene-Related Peptide