title: The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids.
abstract: Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has long been recognized that this 24-hour rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. In the past decade, secondary circadian clocks based on the same molecular machinery as the central master pacemaker were found in other brain areas as well as in most peripheral tissues, including the adrenal glands. Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects. The robust rhythm in circulating glucocorticoid levels has been recognized as a major internal synchronizer of the circadian system. The present review examines the scientific foundation of these novel advances and their implications for health and disease prevention and treatment.
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Henrik
authors.initials: H
authors.lastname: Oster
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Etienne
authors.initials: E
authors.lastname: Challet
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Volker
authors.initials: V
authors.lastname: Ott
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: E Ronald
authors.initials: ER
authors.lastname: de Kloet
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Derk-Jan
authors.initials: DJ
authors.lastname: Dijk
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Stafford
authors.initials: S
authors.lastname: Lightman
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Vgontzas
authors.affiliation: Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Department of Endocrinology and Metabolic Disease (E.R.d.K.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Surrey Sleep Research Center (D.-J.D.), Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XP, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS8 1TH, United Kingdom; Sleep Research and Treatment Center (A.V.), Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033; and Sleep, Metabolism, and Health Center (E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637.
authors.forename: Eve
authors.initials: E
authors.lastname: Van Cauter
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D005938:Glucocorticoids / Q000378:metabolism / Q000502:physiology*; D006801:Humans
chemical_list: D005938:Glucocorticoids