A mathematical model of production, distribution, and metabolism of melatonin in mammalian systems

Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible ''magic bullet'' for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide daily shifts in production controlled by the day/night cycle. The potential for increased disease as a consequence of lower or higher than average production of this hormone has not been well studied, although potential environmental agents may modulate circulating levels (e.g., electric and magnetic fields). In this manuscript, a physiologically realistic mathematical model for the production, distribution, and metabolism of melatonin is developed as a precursor to a future study of the role of chemicals and environmental agents in altering this system. Values for key aspects of the system (e.g., diurnal rates of production of the hormone in the pineal gland) were obtained from the literature and the model was validated against data on circulating levels. The mathematical equations and model parameters are presented. (C) 1997 Academic Press.