Reiter · Frontiers in endocrinology 2024 · narrative review · n=?

Dual sources of melatonin and evidence for different primary functions.

Cited 67 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and mechanistic theoretical reasoning without original human data

PubMed 38808108 · doi:10.3389/fendo.2024.1414463 · record verified 2026-08-31

What was done

Narrative review synthesizing data and conceptual frameworks regarding two distinct biological sources and functional pathways of melatonin in mammals, including humans: pineal versus extrapineal tissue synthesis.

What was found

No primary experimental data, effect estimates, or statistical results are reported in the abstract. The authors speculate that the pineal gland produces less than 5% of total mammalian melatonin in a circadian rhythm released into blood and cerebrospinal fluid for central and peripheral clock regulation. The remaining majority is proposed to be synthesized locally within mitochondria of peripheral tissues in a non-circadian pattern to maintain cellular redox homeostasis and metabolic function.

Why it matters

This review differentiates systemic circadian signaling from local cellular antioxidant mechanisms, providing a theoretical framework for distinct physiological roles of melatonin pools.

Limits

As a narrative review, it presents mechanistic theory and speculation rather than novel empirical or clinical data. Regulating factors and synthesis mechanisms for extrapineal melatonin remain unknown.

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