How the adrenal 'clock' keeps the body in synch

l tissue from normal mice and mice lacking critical clock genes at different time points. While normal adrenal tissue released varying amounts of corticosterone in response to the hormone adrenocorticotropin (ACTH) at different times of day, mutant tissue always released basal levels of hormone. The release of ACTH by the pituitary gland at the base of the brain is driven by a third hormone that is activated by the body's master clock.

The organ-culture experiments suggested that the adrenal contains a circadian clock that defines--or gates--a time window during which the gland most effectively responds to ACTH, Oster said.

"The adrenal clock doesn't appear to drive the rhythm itself but instead regulates the sensitivity of the gland to external stimuli," Oster said. "That gating mechanism provides a level of precision to stabilize circadian rhythms of physiology."

Further evidence from studies in which the researchers transplanted clock mutant adrenal glands into normal mice and normal adrenals into mutant mice reinforced the notion that the adrenal clock determines sensitivity to ACTH. Under conditions of constant darkness, however, mice with normal adrenals that lacked the master clock completely lost the rhythmic corticosterone release, they found, indicating that the adrenal alone cannot sustain the rhythm unless entrained by light.

The circadian network now revealed for the adrenal gland might serve as a "paradigm for the organization of other physiological rhythms," the researchers said.

The findings might also require scientists to do some rethinking, Oster added. Previous studies using organ cultures found that clock gene rhythms can persist for weeks in the absence of external timing signals, leading to the suggestion that peripheral clocks to a large extent operate independently. In marked contrast, the loss of corticosterone rhythm in clock mutant animals with normal adrenals after 2 days in constant da

Contact: Heidi Hardman
Cell Press

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