Assay of melatonin and its metabolites: results in normal and unusual environments

The pineal gland, via its hormone melatonin, is of major importance in the transduction of photoperiodic information in animals. It is concerned both with the synchronisation of annual cycles in photoperiodic mammals and with regulation of circadian rhythmicity in lower vertebrates. Its role, if any, in mammalian circadian systems is still speculative. By analogy with animal work the function of the human pineal is most likely to be concerned with seasonal and circadian rhythms. The study of human pineal function depends heavily on the measurement of melatonin in plasma or urine. Radioimmunoassay (RIA) and gaschromatography-mass-spectrometry (GCMS) have been successfully employed to establish the basic 24-hour rhythm. GCMS has also served to validate RIA. Following early work the reported human plasma levels of melatonin have stabilized approximately at less than 20 pg/ml in daytime with mean night time levels around 40-80 pg/ml. The high sensitivity of GCMS measures daytime levels of 2-5 pg/ml. With confidence established in melatonin assays, its physiological and pathological variations can be investigated in full. Development of assays for urinary melatonin metabolites has made possible the longterm study of circadian variations in different environments. The rhythm of melatonin production can be dissociated from the sleep wake cycle in environmental isolation and behaves like a "strong" oscillator variable. In the unusual social and photoperiodic conditions of Antarctica it remains strongly entrained to the 24 hour day. Whilst measurement of melatonin can provide circumstantial evidence of its function, abolition of its production and its administration in humans can uncover causal relationships. The effects of abolition of the melatonin rhythm by beta-adrenergic antagonists or pinealectomy has not yet been extensively studied in man. Melatonin administration, always (to date), in pharmacological amounts has hypnotic effects in man and may, in some individuals modify the rhythmic characteristics of its own secretion. It remains to be seen whether, in physiological amounts, it is causally related to aspects of human sleep and other circadian or seasonal rhythms.