Cellular and molecular mechanisms mediating melatonin action: A review

Melatonin, the principal hormone of the pineal gland, has been shown to participate in many divergent biological processes. It is recognized that this hormone regulates seasonal reproduction, affects the phasing of mammalian circadian rhythms and modulates retinal functions. More recent evidence indicates additional direct effects on vascular, renal, gonadal and possibly other tissues. This review addresses the known and proposed mechanisms for melatonin actions on the hypothalamic circadian ‘clock’, the anterior pituitary gland, and certain other target organs. The major signalling pathways, through which the recently cloned melatonin receptors operate, appear to be highly variable and tissue-specific, and are examined here in detail. Numerous issues for further evaluation, for example, the proposed role of melatonin in aging, and the therapeutic potential of melatonin, are also critically reviewed.