[Retinal and pineal melatonin--from a circadian signal to therapeutic use].

Melatonin, the major product of the pincal gland, is also synthesized in the retina of several vertebrate species. Retinal melatonin levels show a marked daily variation, with high levels at night and low levels during the light period. Melatonin rhythm generating system includes photodetector, circadian clock and melatonin synthesis machinery and they are located in pincal organ and retina. In both, light regulates daily variations in melatonin secretion by controlling the activity of arylalkylamine N-acetyltransferase (AANAT). In mammals, circadian system is comprised of three major components: the eyes, the hypothalamic suprachiasmatic nucleus (SCN) and the pincal gland. The SCN harbours the endogenous oscillator that is entrained every day to the ambient lighting conditions via retinal input. Among the many circadian rhythms in the body that are driven by SCN output, the synthesis of melatonin in the pincal gland functions as a hormonal message encoding for the duration of darkness. Dissemination of this circadian information relies on the activation of melatonin receptors, which are most prominently expressed in the SCN, and the hypophysical pars tuberalis (PT), but also in many other tissues. Melatonin is essential for rhythmic signaling in the PT. Here, melatonin acts in concert with adenosine to elicit rhythms in clock gene expression. By sensitizing adenylyl cyclase, melatonin opens a temporally-restricted gate and thus lowers the threshold for adenosine to induce cAMP-sensitive genes. This interaction, which regulates gene expression and pituitary output (by endocrine-endocrine interaction) represents general mechanism by which the master clock in the brain synchronizes clock cells in peripheral tissues that require unique phasing of output signals.