Melatonin: Both master clock output and internal time-giver in the circadian clocks network

Sep 15, 2011Journal of physiology, Paris

Melatonin as both a main clock signal and an internal timekeeper in the body’s daily rhythm system

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Abstract

Melatonin, synthesized and released nightly, is controlled by the SCN clock and influences various physiological processes.

The master clock in the hypothalamus is mainly reset by ambient light.
Melatonin acts as a hormonal signal, delivering cues from the SCN to various tissues with melatonin receptors.
In certain tissues, melatonin can induce daily rhythms that are not inherently present.
Melatonin helps synchronize peripheral oscillators, such as those in the fetal adrenal gland.
Endogenous melatonin may provide feedback to the master clock, though its significance requires further study.
Pharmacological melatonin can synchronize the SCN clock and is being investigated for treating circadian, psychiatric, and sleep disorders.

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Daily rhythms in physiological and behavioral processes are controlled by a network of circadian clocks, reset by inputs and delivering circadian signals to the brain and peripheral organs. In mammals, at the top of the network is a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus, mainly reset by ambient light. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the SCN clock and inhibited by light exposure. Several roles of melatonin in the circadian system have been identified. As a major hormonal output, melatonin distributes temporal cues generated by the SCN to the multitude of tissue targets expressing melatonin receptors. In some target structures, like the Pars tuberalis of the adenohypophysis, these melatonin signals can drive daily rhythmicity that would otherwise be lacking. In other target structures, melatonin signals are used for the synchronization (i.e., adjustment of the timing of existing oscillations) of peripheral oscillators, such as the fetal adrenal gland. Due to the expression of melatonin receptors in the SCN, endogenous melatonin is also able to feedback onto the master clock, although its physiological significance needs further characterization. Of note, pharmacological treatment with exogenous melatonin can synchronize the SCN clock. From a clinical point of view, provided that the subject is not exposed to light at night, the daily profile of circulating melatonin provides a reliable estimate of the timing of the human SCN. During the past decade, a number of melatonin agonists have been developed for treating circadian, psychiatric and sleep disorders. These drugs may target the SCN for improving circadian timing or act indirectly at some downstream level of the circadian network to restore proper internal synchronization.

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Melatonin: Both master clock output and internal time-giver in the circadian clocks network

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