ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 26 S8.2

Circadian clock regulation of glucocorticoid synthesis

S Kiessling, G Eichele & H Oster

Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.

Under non-stressed conditions adrenal glucocorticoid (GC) secretion shows strong circadian rhythms with blood levels peaking around wake-up time (i.e. in the morning in humans and at the beginning of the night in nocturnal rodents). These diurnal variations are primarily regulated by rhythmic activation of the hypothalamic–pituitary–adrenal (HPA) axis and the secretion of ACTH from the pituitary. While circadian HPA axis activity is ultimately controlled by the circadian pacemaker residing in the suprachiasmatic nuclei (SCN) of the hypothalamus, we found that clock gene activity at the level of the adrenal cortex regulates the sensitivity of the steroidogenic machinery to ACTH stimulation and, hence, the GC responsiveness during the course of the day. Using a combination of molecular, genetic and surgical approaches we describe the mechanisms of SCN-to-adrenal clock interaction in the regulation of GC rhythms in the mouse. Using a rapid light/dark cycle shifting paradigm we discovered a role for the adrenal clock and adrenal GC rhythms in the re-synchronization of rest-activity cycles during jet lag and devised a novel pharmacological strategy to accelerate jet lag adaptation based on ‘pre-flight’ manipulation of circadian GC secretion.

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