Chronic stress shifts the phase of adrenal clock gene rhythms

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is characterized by a robust circadian rhythm in adrenal secretion of glucocorticoids (GC), driven in part by adrenal clock genes. The GC rhythm serves to synchronize other peripheral clocks and to maintain homeostasis. Mechanisms for entrainment of the adrenal clock remain unclear. Since stress activates the HPA axis, it is possible that entrainment of the adrenal clock and, concomitantly, glucocorticoid rhythms would be susceptible to stress. The present experiment aimed to test the hypothesis that chronic stress can alter adrenal circadian rhythms. The model of chronic subordinate stress used, consisting of daily exposure to a dominant mouse, has shown a robust metabolic phenotype in previous studies. Per2::Luc mice were used to assess rhythmic expression of the clock gene Per2. Per2::Luc mice express a luciferase reporter gene driven by the Per2 promoter, so that light output measured in tissue explants reflects PER2 expression.