Editors' ChoiceCircadian Rhythms

Your Inner Clock Is on Steroids

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Science Translational Medicine  07 Jul 2010:
Vol. 2, Issue 39, pp. 39ec107
DOI: 10.1126/scitranslmed.3001430

Shift work and jet lag are bad for you. They disturb your inner circadian clock(s) and are associated with an increased risk of type 2 diabetes, metabolic syndrome, breast cancer, strokes, and heart disease. Seemingly all tissues in our bodies have the ability to maintain a 24-hour cycle that manifests, for example, as oscillating gene expression. The great synchronizer is a region of the hypothalamus—the suprachiasmatic nucleus (SCN)—that integrates important clues such as light signals from the retina and then realigns our rhythm with day and night. The SCN is also the site that most easily adapts to a resetting of the clock, whereas other organs like the pancreas and liver do so much more slowly. How does this synchronization between the hypothalamus and other organs occur? Kiessling et al. now demonstrate that the adrenal gland's inner clock is quite inert and that the oscillation of glucocorticoids that this gland secretes is a signal that stabilizes clocks in other organs or cells, including those of the SCN.

These authors assessed the oscillations in the expression of five key genes that are important for controlling circadian rhythm in six organs over consecutive time points and multiple days as mice experienced shifts in their exposure to light that modeled jet lag. Ablation of the adrenal gland or pharmacological inhibition of glucocorticoid synthesis allowed clocks in other organs to reset more easily. The inertness of the adrenal clock is probably a stabilizing mechanism that allows us to avoid changing our rhythms just because we saw light at night. Whether we will ever manipulate glucocorticoid levels to relieve jet lag will require additional studies. But it will be interesting to determine whether patients who have lost the ability to secrete glucocorticoids because of adrenal insufficiency, a condition former President Kennedy suffered from, have an easier time overcoming jet lag.

S. Kiessling et al., Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag. J. Clin. Invest. 120, 2600–2609 (2010). [Full Text]

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