Human plasma melatonin and urinary 6-sulphatoxy melatonin: studies in natural annual photoperiod and in extended darkness.

OBJECTIVES: The aims of the study were (1) to examine the human plasma melatonin rhythm at the equinoxes and the solstices in the natural photoperiod (at 35 degrees S); (2) to examine melatonin rhythms in the same subjects under extended darkness conditions to expose any suppressive (gating) effects of light at any time of the year; (3) to undertake a rigorous examination of the relationship between plasma melatonin and the urinary metabolite 6-sulphatoxy melatonin at varying times of the year. DESIGN: At the equinoxes and solstices, unrestricted subjects had hourly urine collections followed by venous blood sampling taken under natural light conditions for 24 hours. Following a 24 hour interval, a similar collection regime was performed with subjects held under conditions of extended darkness (5 hours darkness prior to natural sunset and following natural sunrise) for a further 24 hours. SUBJECTS: Groups of four (minimum) to six female volunteers (age range 18-35 years) were studied, who had a normal lifestyle, no history of depression, and were not taking any medication or recently engaged in shiftwork. MEASUREMENTS: The plasma was assayed for melatonin and the urine samples for 6-sulphatoxy melatonin by radioimmunoassay. RESULTS: The onset of natural melatonin secretion was delayed until after sunset at all seasons but was earlier in summer, and not different from the time of sunset in extended darkness. The offset of melatonin secretion under natural conditions occurred at sunrise in autumn and winter but was delayed until after sunrise during spring and summer, particularly in extended darkness. No significant changes in the duration of melatonin secretion were observed between seasons nor between the duration of melatonin secretion under natural photoperiod or extended darkness. The measurement of 6-sulphatoxy melatonin proved to be a close indicator of the phase and amplitude of secretion of plasma melatonin. Both onset and offset times of 6-sulphatoxy melatonin were delayed compared to the times when plasma melatonin was detectable/undetectable. A good correlation exists between the total plasma melatonin secretion and that of 6-sulphatoxy melatonin. CONCLUSIONS: The results suggest evidence for a suppressive (gating) effect of light at dawn only during summer which was associated with a phase advance of the onset of melatonin secretion at this time of year. The lack of a major gating effect of environment light on melatonin secretion, and the unchanging duration of secretion through the year in the normally entrained human, highlight differences between the human and those photoperiodic animal species which breed seasonally. Urinary 6-sulphatoxy melatonin proved to be a good indicator of plasma melatonin levels under rigorous examination and is confirmed as a useful clinical measure.