Human circadian system outline

Melatonin (upper right inset) is produced in the pineal gland. The production and secretion of melatonin is mediated largely by postganglionic retinal nerve fibers that pass through the retinohypothalamic tract to the suprachiasmatic nucleus, through the superior cervical ganglion, and finally to the pineal gland. This neuronal system is activated by darkness and suppressed by light (left insets). The activation of alpha1 and beta1 adrenergic receptors in the pineal gland raises cyclic AMP and calcium concentrations and activates arylalkylamine N-acetyltransferase, initiating the synthesis and release of melatonin. The daily rhythm of melatonin secretion is controlled by the endogenous master pacemaker located in the SCN, whereas timing in the SCN is in turn regulated by melatonin. The lower right inset shows the temporal relationship between the activity of the suprachiasmatic nuclei and the secretion of melatonin within a period of 24 hours (not to scale). (Adapted 2006, with permission, from: Brzezinski A. Mechanisms of disease: melatonin in humans. New Engl J Med 1997;336:186-195. Copyright © 1997 Massachusetts Medical Society.)