title: The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats.
abstract: Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood-brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day.
authors.affiliation: Departamento De Biología Celular y Fisiología, Instituto De Investigaciones Biomédicas, Universidad Nacional Autónoma De México , 04510 Mexico City, Mexico.
authors.forename: Luis
authors.identifier: 0000-0001-6362-7968
authors.initials: L
authors.lastname: Leon-Mercado
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands; Department of Endocrinology and Metabolism, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Daniela
authors.identifier: 0000-0001-8406-1377
authors.initials: D
authors.lastname: Herrera Moro Chao
authors.affiliation: Departamento De Biología Celular y Fisiología, Instituto De Investigaciones Biomédicas, Universidad Nacional Autónoma De México , 04510 Mexico City, Mexico.
authors.forename: María Del Carmen
authors.identifier: 0000-0002-5932-9148
authors.initials: MD
authors.lastname: Basualdo
authors.affiliation: Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; School of Health Sciences, Bukkyo University, Kyoto 603-8301, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
authors.affiliation: Departamento De Anatomía, Facultad De Medicina, Universidad Nacional Autónoma De México , 04510 Mexico City, Mexico.
authors.forename: Carolina
authors.initials: C
authors.lastname: Escobar
authors.affiliation: Departamento De Biología Celular y Fisiología, Instituto De Investigaciones Biomédicas, Universidad Nacional Autónoma De México , 04510 Mexico City, Mexico.
authors.forename: Ruud M
authors.identifier: 0000-0003-3894-4632
authors.initials: RM
authors.lastname: Buijs
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D011965:Receptors, Glucocorticoid; D003345:Corticosterone
keywords: ACTH; arcuate; glucocorticoid receptor; glucocorticoids; negative feedback; paraventricular nucleus 