Melatonin
Also known as: N-acetyl-5-methoxytryptamine, hormone of darkness
An indoleamine derived from tryptophan and secreted by the pineal gland at night under the control of the suprachiasmatic clock; it signals darkness, promotes sleep and helps entrain circadian rhythms.
Overview
Melatonin synthesis follows the light–dark cycle. In darkness, the SCN releases its inhibition of the paraventricular nucleus, sympathetic fibres from the superior cervical ganglion release norepinephrine onto pinealocyte β1 (and α1) receptors, cAMP rises and the rate-limiting enzyme arylalkylamine N-acetyltransferase (AANAT) increases many-fold, converting serotonin to N-acetylserotonin, which ASMT (HIOMT) methylates to melatonin. Light at night — especially blue light — rapidly suppresses synthesis.
Melatonin is not stored; it diffuses straight into the blood and CSF. It acts on MT1 and MT2 receptors (Gi): MT1 in the SCN reduces neuronal firing and promotes sleep propensity, MT2 shifts the phase of the clock. It also lowers core body temperature and has antioxidant properties. It is metabolised in the liver (CYP1A2) to 6-sulfatoxymelatonin, excreted in urine. Night-time levels are highest in childhood and fall with age.
- Location
Source: pinealocytes of the pineal gland (smaller amounts in retina and gut). Targets: SCN, pars tuberalis of the pituitary, many peripheral tissues.
Function
- Signals the duration of darkness (internal "night").
- Promotes sleep onset and lowers core temperature.
- Phase-shifts and entrains circadian rhythms.
- Influences seasonal reproduction in animals; may modulate puberty timing in humans.
- Physiology
Class: indoleamine (tryptophan-derived amine). Receptors: MT1, MT2 — Gi. Half-life ≈20–50 min. Peak ≈02:00–04:00; dim-light melatonin onset ≈2 h before habitual sleep.
- Regulation
Darkness (via SCN → PVN → spinal cord → superior cervical ganglion → norepinephrine) stimulates; light suppresses. β-blockers reduce nocturnal melatonin.
Clinical significance
Therapeutic melatonin
Used for jet lag, delayed sleep–wake phase disorder, insomnia in older adults and children with neurodevelopmental disorders, and non-24-hour rhythm in blindness. Timing matters: evening doses advance the clock.
Inverted melatonin rhythm
In Smith–Magenis syndrome melatonin is secreted by day, causing daytime sleepiness and night waking.
Test yourself
Light suppresses melatonin secretion through which pathway?
- Optic nerve → lateral geniculate body → visual cortex → pineal
- Retina → retinohypothalamic tract → suprachiasmatic nucleus → paraventricular nucleus → spinal cord → superior cervical ganglion → pineal
- Retina → superior colliculus → posterior commissure → pineal
- Retina → oculomotor nucleus → ciliary ganglion → pineal
Answer: Retina → retinohypothalamic tract → suprachiasmatic nucleus → paraventricular nucleus → spinal cord → superior cervical ganglion → pineal
Melanopsin-containing retinal ganglion cells signal the SCN, which via the PVN and upper thoracic preganglionic neurons controls postganglionic sympathetic fibres from the superior cervical ganglion. Norepinephrine on pinealocyte β1 receptors (in darkness) drives AANAT and melatonin synthesis.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.