Resetting of Circadian Time in Peripheral Tissues by Glucocorticoid Signaling

TLDR

Mammalian circadian oscillators exist in both the central suprachiasmatic nucleus and most peripheral tissues. Dexamethasone induces circadian gene expression in fibroblasts and transiently shifts phase in liver, kidney, and heart but not in SCN neurons, enabling a phase‑shift response curve that shows peripheral clocks remain resettable throughout the day.

Abstract

In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.