title: Estradiol regulates effects of hindbrain activator 5-aminoimidazole-4-carboxamide-riboside administration on hypothalamic adenosine 5'-monophosphate-activated protein kinase activity and metabolic neurotransmitter mRNA and protein expression.
abstract: Hindbrain adenosine 5'-monophosphate-activated protein kinase (AMPK) activation alters hypothalamic neuronal genomic activity in an estradiol (E)-dependent manner. This study examines the premise that E regulates metabolic effector neuron reactivity to hindbrain AMPK. Paraventricular (PVH), arcuate (ARH), and ventromedial (VMH) nuclei were micropunched from brains of E- or oil (O)-implanted ovariectomized female rats that had been injected, into the fourth ventricle, with the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR; A) or saline (S) and analyzed by quantitative polymerase chain reaction and Western blotting for neurotransmitter mRNA and protein expression. PVH corticotrophin-releasing hormone gene and protein profiles were decreased in O/A and E/A animals. ARH pro-opiomelanocortin (POMC) mRNA and protein were both elevated in O/A but were diminished or unchanged, respectively, in E/A animals; ARH neuropeptide Y (NPY) transcription was inhibited in O/A and E/A animals, but neuropeptide content was augmented in E/A only. VMH SF-1 mRNA and protein were reduced in O and E animals. AICAR did not alter AMPK protein in any structure but elevated PVH (↑E), did not alter ARH, and decreased VMH (↓O,↓E) pAMPK. Results demonstrate hypothalamic metabolic neurotransmitter and AMPK reactivity to hindbrain AMPK activation, including E-dependent adjustments in POMC and NPY transcription and protein expression. Dissimilar POMC (↑O vs. ↔E) and NPY (↓O vs. ↑E) neuropeptide responses to caudal fourth ventricle AICAR indicate E regulation of hindbrain AMPK signaling and/or target receptivity, implying that ARH-controlled metabolic responses may differ in the presence vs. absence of E. Evidence for variable changes in hypothalamic AMPK activity resulting from hindbrain sensor manipulation suggests that individual (or region-based groups of) AMPK-expressing neuron populations are uniquely impacted by hindbrain AMPK.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, Louisiana.
authors.forename: Fahaad S H
authors.initials: FS
authors.lastname: Alenazi
authors.forename: Baher A
authors.initials: BA
authors.lastname: Ibrahim
authors.forename: Karen P
authors.initials: KP
authors.lastname: Briski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003348:Cortisone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000235:genetics* / Q000378:metabolism*; D010052:Ovariectomy; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides / Q000008:administration & dosage*; D012265:Ribonucleotides / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D012263:Ribonucleosides; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D004958:Estradiol; C011651:acadesine; D011333:Pro-Opiomelanocortin; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose; D003348:Cortisone
keywords: AICAR; SF-1; Western blot; neuropeptide Y; pAMPK; pro-opiomelanocortin