In mammals, including humans, a master clock in the brain and subordinate clocks found in organs throughout the body coordinate daily, or circadian, rhythms of behavior and physiology.
Now, researchers reporting in the August Cell Metabolism, published by Cell Press, have elucidated the role of clocks of the adrenal glands in keeping those physiologic and metabolic rhythms in synchrony.
The adrenal glands sit atop each kidney, where they discharge steroid hormones known as corticoids--including the stress-related hormones adrenaline and cortisol. Corticoids influence stress response, metabolism, mineral balance, and reproduction.
In a study of mice, Henrik Oster of the Wellcome Trust Centre for Human Genetics at the University of Oxford, Gregor Eichele at the Max Planck Institute of Biophysical Chemistry, and colleagues found that the adrenal clock acts as a "gate," shaping the amount of corticosterone--the mouse equivalent of cortisol--secreted in response to other hormonal cues driven by the body's master clock.
"The adrenal clock is of particular interest since adrenal corticoids have been implicated in the synchronization of subordinated clocks and were demonstrated to control metabolic rhythms in many other organs, including liver, kidney, and brain," Oster said. "We've identified a mechanism that bridges the gap between peripheral clock gene oscillations and the control of corticoid-dependent physiological rhythms in the adrenal gland and possibly in many other organs."
Oster's team found that the majority of clock genes exhibit a circadian pattern of activity in the adrenal. The clock genes were strongly expressed specifically in outer layers of the adrenal gland that are responsible for corticoid production. The findings offered "bona fide evidence" for the presence of a peripheral circadian clock in the adrenal glands.
To find out how the adrenal clock ticks, the researchers first treated slices of adrenal 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.