Temporal organization of pineal melatonin signaling in mammals.

In mammals, the pineal gland is the sole endocrine source of melatonin, which is secreted according to daily and seasonal patterns. This mini-review synthesizes the established endocrine actions of melatonin in the following temporal contexts. Melatonin is a strictly regulated output of the circadian timing system, but under certain conditions, may also entrain the circadian pacemaker and clocks in peripheral tissues. As the waveform of nightly melatonin secretion varies seasonally, melatonin provides a hormonal representation of the time of year. The duration of elevated melatonin secretion regulates reproductive physiology and other seasonal adaptations either by entraining a circannual rhythm or by inducing seasonal responses directly. An entrainment action of nightly melatonin on clock gene expression in the pars tuberalis of the anterior pituitary may partly underly its mechanistic role as a photoperiodic switch. Melatonin has important functions developmentally to regulate multiple physiological systems and program timing of puberty. Endogenous melatonergic systems are disrupted by modern lifestyles of humans through altered circadian entrainment, acute suppression by light and self-administration of pharmacological melatonin. Non-endocrine actions of locally synthesized melatonin fall outside of the scope of this mini-review.