title: Involvement of neuropeptide Y Y1 receptors in the regulation of neuroendocrine corticotropin-releasing hormone neuronal activity.
abstract: The neuroendocrine parvocellular CRH neurons in the paraventricular nucleus (PVN) of the hypothalamus are the main integrators of neural inputs that initiate hypothalamic-pituitary-adrenal (HPA) axis activation. Neuropeptide Y (NPY) expression is prominent within the PVN, and previous reports indicated that NPY stimulates CRH mRNA levels. The purpose of these studies was to examine the participation of NPY receptors in HPA axis activation and determine whether neuroendocrine CRH neurons express NPY receptor immunoreactivity. Infusion of 0.5 nmol NPY into the third ventricle increased plasma corticosterone levels in conscious rats, with the peak of hormone levels occurring 30 min after injection. This increase was prevented by pretreatment with the Y1 receptor antagonist BIBP3226. Immunohistochemistry showed that CRH-immunoreactive neurons coexpressed Y1 receptor immunoreactivity (Y1r-ir) in the PVN, and a majority of these neurons (88.8%) were neuroendocrine as determined by ip injections of FluoroGold. Bilateral infusion of the Y1/Y5 agonist, [leu(31)pro(34)]NPY (110 pmol), into the PVN increased c-Fos and phosphorylated cAMP response element-binding protein expression and elevated plasma corticosterone levels. Increased expression of c-Fos and phosphorylated cAMP response element-binding protein was observed in populations of CRH/Y1r-ir cells. The current findings present a comprehensive study of NPY Y1 receptor distribution and activation with respect to CRH neurons in the PVN. The expression of NPY Y1r-ir by neuroendocrine CRH cells suggests that alterations in NPY release and subsequent activation of NPY Y1 receptors plays an important role in the regulation of the HPA.
authors.affiliation: Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Dimitrov
authors.forename: M Regina
authors.initials: MR
authors.lastname: DeJoseph
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brownfield
authors.forename: Janice H
authors.initials: JH
authors.lastname: Urban
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism*; D020542:Third Ventricle
chemical_list: D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D015415:Biomarkers; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat