Oral 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

The role of adrenal glucocorticoids in circadian resynchronisation and stability in mice (#12)

Pureum Kim 1 , Warrick Inder 2 3 , Oliver Rawashdeh 1
  1. School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia
  2. Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
  3. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, QLD, Australia

The circadian system is a 24-h timing system that generates rhythms in behaviour and physiology and maintains their proper alignment to geophysical time. Adrenal glucocorticoids are important peripheral endocrine hormones that are rhythmically synthesised and released by the adrenals under the regulation of the central master circadian clock. The daily-timed release of glucocorticoids (corticosterone in rodents) suggests that the adrenals transmit information about daytime to its many targets within the body, and thus, maintaining the proper alignment of physiology and behaviour. One core clock gene, Period1 (Per1), is involved in the regulation of corticosterone release. Its induction in the adrenal cortex results in rapid release of corticosterone when light is abruptly introduced. Per1 also plays an important role in circadian clock resetting by light. Using a Per1-knockout mouse model, we aimed to investigate the role of Per1 in glucocorticoids regulation, specifically, its role in circadian clock resetting of central-controlled rhythms (e.g. sleep/wake rhythms and metabolism) by subjecting mice to an experimental jet-lag paradigm. Per1-deficient mice showed normal rhythmic corticosterone secretion under standard 12:12 hour light:dark conditions but demonstrated prominently accelerated resynchronisation of both behaviour and corticosterone rhythm in response to the 12hr jet-lag. To further clarify whether rapid circadian clock resetting in Per1-deficient mice is attributed to corticosterone rhythm, we studied mice after bilateral adrenalectomy. Corticosterone deficiency further facilitated a more rapid resynchronisation of the circadian system in both wild-type and Per1-deficient mice. These data suggest that the absence of Per1 in the adrenals does not contribute the accelerated central clock resetting but rhythmic Per1 and glucocorticoids reinforce the resistance of the circadian system to abrupt changes in photoperiod and enhance circadian stability. Extrapolating to humans, shift workers and international travellers may adapt to work roster/time zone changes more rapidly in the presence of reduced Per1 and glucocorticoid activity.