Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

A radioimmunoassay has been developed for the major metabolite of melatonin, 6-suIphatoxymelatonin (aMT6s). The assay is specific, sensitive and is direct for both urine and plasma samples. Classical validation procedures have been employed and the urinary assay has been compared with an established gas chromatographic/mass spectrometric assay. A number of physiological studies have been carried out. A marked diurnal rhythm in both urinary and plasma aMT6s excretion was found which correlated closely with plasma melatonin values. There were large inter-individual variations in aMT6s excretion but its production was consistent for any one volunteer over a four-day period. No evidence was obtained for the episodic secretion of melatonin or aMT6s when blood samples were taken every thirty seconds for ten minutes. Administration of a peripheral B-blocker to volunteers, resulted in the abolition of the night-time rise in aMT6s excretion. In a seasonal study, a small but highly significant change in the acrophase of the aMT6s rhythm was found during the year with a phase advance in summer compared to winter. Changes in aMT6s excretion with age were also investigated. Total urinary aMT6s excretion was relatively constant in forty children aged 2-20 years. However, when aMT6s excretion was expressed as a function of body weight highly significant age-related changes were observed. In ninety adult volunteers aged 20-80 years there was a significant decline in total 24h aMT6s excretion with age, with significantly lower excretion in elderly subjects. No relationships were found between total 24h aMT6s excretion and body weight, height or pineal calcification. In addition to the above physiological studies, the pharmacokinetics of melatonin and aMT6s were investigated following the oral administration of melatonin to normal volunteers.