The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects. (20th October 2016)

• Record Type: Journal Article
• Authors: Yurtsever, Türkan; Schilling, Thomas M.; Kölsch, Monika; Turner, Jonathan D.; Meyer, Jobst; Schächinger, Hartmut; Schote, Andrea B.
• Is Part Of: Chronobiology international. Volume 33:Number 9(2016)
• Page Start: 1222
• Page End: 1234
• Publication Date: 2016-10-20
• Subjects: PERIOD genes -- circadian clock -- HPA axis -- hydrocortisone -- healthy subjects; Chronobiology -- Periodicals; Biological rhythms -- Periodicals; Circadian rhythms -- Periodicals; 571.77
• DOI: 10.1080/07420528.2016.1211668
• Languages: English
• ISSNs: 0742-0528

Abstract

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.