# Melatonin Physiology > Melatonin physiology for MBBS Physiology: pineal synthesis, light pathway via SCN, night peak levels, receptors and clinical uses. - Canonical URL: https://prepelephant.com/topics/mbbs/physiology/melatonin-physiology - Exam / course: MBBS · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Melatonin Physiology", PrepElephant, https://prepelephant.com/topics/mbbs/physiology/melatonin-physiology ## Direct answer Darkness, relayed from the retina to the pineal gland, is the sole physiological stimulus for melatonin secretion: plasma levels rise from a daytime baseline near 5-20 pg/mL to a night peak of roughly 60-200 pg/mL between 2 and 4 AM, then fall again, with a plasma half-life of only 30-60 minutes. The synthetic chain inside pinealocytes runs serotonin to N-acetylserotonin via arylalkylamine N-acetyltransferase (AANAT, the rate-limiting enzyme) and then to melatonin via ASMT. Light reaches the gland through a fixed polyneuronal route — retina, retinohypothalamic tract, suprachiasmatic nucleus, paraventricular nucleus, intermediolateral column T1-T2, superior cervical ganglion — which is why lesions anywhere along it abolish the rhythm. Exogenous melatonin in 0.5-5 mg doses is used to rephase rhythms in jet lag and non-24-hour disorder of the blind. ## What you must remember - **Synthesis sequence:** L-tryptophan, serotonin, N-acetylserotonin (AANAT — rate-limiting, induced 10-fold or more at night), melatonin (ASMT/HIOMT); the pineal concentrates serotonin beyond any other tissue. - **Light pathway in full:** photoreceptors or melanopsin ganglion cells, retinohypothalamic tract, suprachiasmatic nucleus (SCN), PVN, descending fibres to the intermediolateral column at T1-T2, superior cervical ganglion, postganglionic noradrenergic fibres to pinealocytes acting on beta-1 receptors. - **Numbers:** night peak 60-200 pg/mL at 2-4 AM in young adults, daytime under about 20 pg/mL, half-life 30-60 minutes; secretion declines steeply with age — pineal calcification is near-universal by the sixth decade. - **Receptors:** MT1 (sleep induction) and MT2 (phase shifting) — G-protein coupled, acting through Gi to reduce cAMP; ramelteon is a selective agonist. - **Clinical dosing logic:** 0.5 mg shifts phase, 2-5 mg hypnotic; for eastward jet lag, take it at local bedtime on arrival; the blind with non-24-hour disorder are the clearest indication. - **Pineal region tumours:** compress the tectum producing Parinaud syndrome — vertical gaze palsy, light-near dissociation of pupils — a classic neuro-ophthalmology link. - **Vegetative marker:** melatonin is the hormonal hand of the SCN — measuring its rhythm (or its urinary metabolite 6-sulphatoxymelatonin) is how circadian phase is assessed objectively. ## How the rhythm is built and broken Start with a healthy volunteer in constant dim light: melatonin still rises each evening, because the SCN generates the rhythm endogenously — light only entrains it. The onset of melatonin secretion in dim light (DLMO) occurs about 2 hours before habitual sleep and is the reference marker of circadian phase. Now expose the volunteer to bright light at 10 PM: the onset is pushed later, a phase delay. Bright light at 5 AM does the opposite, advancing the clock — the asymmetry exploited in jet lag and delayed sleep phase protocols. Then take shift work: a night-duty doctor under bright ward lighting suppresses melatonin acutely, then sleeps in a lit morning bedroom while the rhythm drifts. Chronic mismatch of this kind degrades sleep, glucose control and alertness. The blind patient carries the extreme case — without retinal input the SCN free-runs at its intrinsic period slightly above 24 hours, so sleep drifts in and out of alignment with the clock day; low-dose melatonin at a fixed bedtime is the one therapy that anchors the rhythm, a beautiful example of physiology prescribing itself. ## Where students slip Students say light stimulates melatonin — it is darkness, with light inhibiting secretion through the sympathetic chain; the viva probe is to name every station from retina to pineal, and the T1-T2 intermediolateral relay is where most answers fail. The second error is calling melatonin a sleeping tablet: it is a chronobiotic — a phase shifter — so timing matters more than dose, and taking it in the morning can shift rhythms the wrong way. A third slip is forgetting that the pineal is outside the blood-brain barrier and lies at the posterior third ventricle, so pineal tumours present with hydrocephalus and Parinaud gaze signs, not endocrine syndromes. ## Frequently asked questions ### Which enzyme is rate-limiting in melatonin synthesis? Arylalkylamine N-acetyltransferase (AANAT), which converts serotonin to N-acetylserotonin and rises many-fold at night under noradrenergic control from the superior cervical ganglion. ### How does light information reach the pineal gland? Through the retinohypothalamic tract to the suprachiasmatic nucleus, then via the paraventricular nucleus and intermediolateral column T1-T2 to the superior cervical ganglion, whose noradrenergic fibres innervate the pinealocytes. ### What are normal melatonin levels by time of day? Daytime plasma levels are near 5-20 pg/mL, rising to a peak of roughly 60-200 pg/mL between 2 and 4 AM in young adults, with secretion declining markedly with age. ### Which melatonin receptor does ramelteon act on? Ramelteon is a selective MT1 and MT2 agonist used for sleep-onset insomnia, avoiding the receptor promiscuity that limits melatonin's own hypnotic use. ### Why is melatonin used in non-24-hour sleep-wake disorder? Blind patients cannot entrain the SCN by light, so their rhythm free-runs slightly longer than 24 hours; correctly timed melatonin entrains the clock pharmacologically, realigning sleep with the solar day.