melatonin

Melatonin is synthesized in the pineal gland from tryptophan, which is first converted to serotonin, then to melatonin via N-acetylation and O-methylation. Its release is controlled by the suprachiasmatic nucleus (SCN) of the hypothalamus, which receives light input from the retinohypothalamic tract; light suppresses melatonin secretion (via inhibition of the SCN-to-pineal pathway involving the superior cervical ganglion and norepinephrine release), while darkness promotes it. Melatonin secretion follows a circadian pattern, rising in the evening, peaking in the middle of the night, and declining before dawn. It acts on MT1 and MT2 receptors (Gi-coupled) in the SCN and other tissues to promote sleep onset and help synchronize the internal circadian clock with the external light-dark cycle. Clinically, melatonin is used to treat circadian rhythm disorders such as jet lag, shift-work disorder, delayed sleep phase syndrome, and sometimes insomnia in the elderly or in blind individuals lacking light input. Melatonin secretion decreases with age, which may contribute to sleep disturbances in older adults. It also has antioxidant properties and may have a role in immune modulation, though these are less clinically emphasized for boards. Pineal gland tumors (pinealomas) can affect melatonin levels and cause precocious puberty due to loss of melatonin's inhibitory effect on gonadotropin-releasing hormone (GnRH). Key associations for exams: pineal gland = melatonin source; SCN = circadian pacemaker; light suppresses secretion; used for jet lag and circadian rhythm disorders; synthesized from tryptophan → serotonin → melatonin.