title: The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects.
abstract: The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression. Forty participants (50% males and 50% females) were randomly assigned to groups receiving a saline placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was drawn every 15 min to measure quantitative gene expression of PER1, PER2 and PER3. A potential role of the GR was determined by an ex vivo study stimulating whole blood with hydrocortisone and RU486 (a GR antagonist). As a result, moderate doses of hydrocortisone produced an acute and temporary induction of PER1 and PER3 mRNA levels, whereas PER2 was not responsive to the hormone administration. The cortisol-dependent induction of PER1 was blocked by the GR antagonist in whole blood after treatment with hydrocortisone and RU486 ex vivo. In conclusion, acute pharmacological stress modulated the expression of PER1 and PER3 in whole blood temporarily in our short-term sampling design, suggesting that these circadian genes mediate stable molecular mechanisms in the periphery.
authors.affiliation: a Department of Neurobehavioral Genetics , Institute of Psychobiology, University of Trier , Trier , Germany.
authors.forename: Türkan
authors.initials: T
authors.lastname: Yurtsever
authors.affiliation: b Department of Clinical Psychophysiology , Institute of Psychobiology, University of Trier , Trier , Germany.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schilling
authors.affiliation: b Department of Clinical Psychophysiology , Institute of Psychobiology, University of Trier , Trier , Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Kölsch
authors.affiliation: c Department of Infection and Immunity , Luxembourg Institute of Health, Esch-sur-Alzette, Grand-Duchy of Luxembourg.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Turner
authors.affiliation: a Department of Neurobehavioral Genetics , Institute of Psychobiology, University of Trier , Trier , Germany.
authors.forename: Jobst
authors.initials: J
authors.lastname: Meyer
authors.affiliation: b Department of Clinical Psychophysiology , Institute of Psychobiology, University of Trier , Trier , Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schächinger
authors.affiliation: a Department of Neurobehavioral Genetics , Institute of Psychobiology, University of Trier , Trier , Germany.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Schote
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D015735:Mifepristone; D006854:Hydrocortisone
keywords: HPA axis; PERIOD genes; circadian clock; healthy subjects; hydrocortisone