CIRCADIAN-RHYTHM OF FREE MELATONIN IN HUMAN PLASMA

The appearance of melatonin in saliva in concentrations up to 70% lowe r than those in blood has led to the suggestion that melatonin is boun d to plasma protein and that saliva levels reflect the circulating fre e hormone. To test this directly, melatonin was measured in human plas ma from 10 subjects after ultrafiltration through Centrifree micropart ition tubes and compared to saliva melatonin levels in samples collect ed simultaneously. Melatonin was detected in the protein-free fraction and increased throughout the night in parallel with the saliva melato nin level. Peak concentrations ranged from 45-200 pmol/L (mean +/- SEM , 106 +/- 17 pmol/L) and averaged 23% of the total melatonin level. Ac ross all samples, the correlation between the saliva levels and the fr ee hormone levels was significant (r = 0.84; P < 0.05). These results provide the first direct evidence that endogenous melatonin is bound t o plasma proteins and that saliva melatonin generally reflects the lev els of this binding.