title: Glucose responsiveness in a novel adult-derived GnRH cell line, mHypoA-GnRH/GFP: involvement of AMP-activated protein kinase.
abstract: Glucose regulates energy homeostasis and reproductive function within the hypothalamus. The underlying mechanisms responsible for glucose regulation of GnRH gene transcription were investigated using a novel murine immortalized, adult-derived hypothalamic cell line, mHypoA-GnRH/GFP. Analysis of GnRH mRNA synthesis and secretion following agonist treatment demonstrated that the mHypoA-GnRH/GFP cell line is a representative model of in vivo GnRH neurons. c-fos mRNA levels, following glucose exposure, indicated that these neurons were responsive to low (0.5mM) and high (5mM) glucose, and high glucose stimulated GnRH mRNA transcription in a metabolism-dependent manner. Glucose inhibited AMPK activity, and was linked to the downstream stimulation of GnRH mRNA levels. The effect was confirmed with an AMPK antagonist, Compound C. Collectively, these findings demonstrate that glucose can directly regulate GnRH transcription, while implicating the AMPK pathway as an essential mediator of nutritional signaling in a novel GnRH neuronal cell model.
authors.affiliation: Department of Physiology, University of Toronto, University Health Network, Toronto, ON M5S 1A8, Canada.
authors.forename: Sean A
authors.initials: SA
authors.lastname: McFadden
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Menchella
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chalmers
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Centeno
authors.forename: Denise D
authors.initials: DD
authors.lastname: Belsham
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009474:Neurons; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010455:Peptides; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D005576:Colforsin; D009569:Nitric Oxide; D007987:Gonadotropin-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate
keywords: AMPK; Glucose; Gonadotropin-releasing hormone; Hypothalamus; Neuropeptide