title: MAP kinases couple hindbrain-derived catecholamine signals to hypothalamic adrenocortical control mechanisms during glycemia-related challenges.
abstract: Physiological responses to hypoglycemia, hyperinsulinemia, and hyperglycemia include a critical adrenocortical component that is initiated by hypothalamic control of the anterior pituitary and adrenal cortex. These adrenocortical responses ensure appropriate long-term glucocorticoid-mediated modifications to metabolism. Despite the importance of these mechanisms to disease processes, how hypothalamic afferent pathways engage the intracellular mechanisms that initiate adrenocortical responses to glycemia-related challenges are unknown. This study explores these mechanisms using network- and cellular-level interventions in in vivo and ex vivo rat preparations. Results show that a hindbrain-originating catecholamine afferent system selectively engages a MAP kinase pathway in rat paraventricular hypothalamic CRH (corticotropin-releasing hormone) neuroendocrine neurons shortly after vascular insulin and 2-deoxyglucose challenges. In turn, this MAP kinase pathway can control both neuroendocrine neuronal firing rate and the state of CREB phosphorylation in a reduced ex vivo paraventricular hypothalamic preparation, making this signaling pathway an ideal candidate for coordinating CRH synthesis and release. These results establish the first clear structural and functional relationships linking neurons in known nutrient-sensing regions with intracellular mechanisms in hypothalamic CRH neuroendocrine neurons that initiate the adrenocortical response to various glycemia-related challenges.
authors.affiliation: Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA. amkhan2@utep.edu
authors.forename: Arshad M
authors.initials: AM
authors.lastname: Khan
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Kaminski
authors.forename: Graciela
authors.initials: G
authors.lastname: Sanchez-Watts
authors.forename: Todd A
authors.initials: TA
authors.lastname: Ponzio
authors.forename: J Brent
authors.initials: JB
authors.lastname: Kuzmiski
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
authors.forename: Alan G
authors.initials: AG
authors.lastname: Watts
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D003847:Deoxyglucose