I Introduction UNTIL 35 yr ago, most scientists did not take research on the pineal gland seriously The decade beginning in 1956, however, provided several discoveries that laid the foundation for what has become a very active area of investigation These important early observations included the findings that, 1), the physiological activity of the pineal is influenced by the photoperiodic environment (1–5); 2), the gland contains a substance, N-acetyl-5-methoxytryptamine or melatonin, which has obvious endocrine capabilities (6, 7); 3), the function of the reproductive system in photoperiodically dependent rodents is inextricably linked to the physiology of the pineal gland (5, 8, 9); 4), the sympathetic innervation to the pineal is required for the gland to maintain its biosynthetic and endocrine activities (10, 11); and 5), the pineal gland can be rapidly removed from rodents with minimal damage to adjacent neural structures using a specially designed trephine (12) Since the mid 1960s, research on t

Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*

The significance of the metabolism of the neurohormone melatonin: Antioxidative protection and formation of bioactive substances

An assessment of the rhythmic characteristics of melatonin secretion in man and other species requires the determination of 24-h secretion profiles. Measurement of a major excreted metabolite would allow noninvasive study of pineal function, applicable in particular to pediatric and long term circadian rhythm studies. This report describes a simple and rapid RIA for 6-hydroxymelatonin sulfate in human plasma and urine. Physiological studies revealed that both plasma and urinary levels of 6-hydroxymelatonin sulfate were closely related to plasma melatonin, and that the urinary 24-h rhythm was abolished by the beta 1-adrenergic anagonist atenolol.

Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: abolition of the urinary 24-hour rhythm with atenolol.

A radioimmunoassay (RIA) for urinary 6-sulphatoxymelatonin (aMT6s) using an 125I-aMT6s tracer is described. Iodinated aMT6s used as the label was synthesised by direct iodination of aMT6s using 1,3,4,6 tetrachloro 3,6 diphenylglycouril as the oxidant. The assay shows low cross reactivity with related compounds. Serial dilutions of 1:250 and 1:125 diluted urine gave parallel displacement curves. Comparison of the new RIA using 125I-aMT6s with the RIA using 3H-aMT6s label gave good correlation, as did comparison with a gas chromatography mass spectroscopy (GCMS) for total free and conjugated 6-hydroxymelatonin.

Radioimmunoassay for 6-sulphatoxymelatonin in urine using an iodinated tracer.

Comparing a direct radioimmunoassay for 6-sulfatoxymelatonin (aMT6s) with an established gas chromatographic/mass spectrometric method for 6-hydroxymelatonin, we found a good correlation r = 0.94 (P less than 0.001, n = 100). aMT6s was stable, both in urine and plasma samples, without preservative, for at least two years at -20 degrees C and for five days at room temperature. Urinary excretion of aMT6s showed considerable inter-individual differences; however, the aMT6s excretion of any one individual was consistent over a four-day period, as assessed by continuous collection from 18 normal volunteers. Total 24-h urinary excretion of aMT6s was significantly correlated with the area under the curve of the respective profiles for plasma melatonin (r = 0.75, P = 0.0002) and plasma aMT6s (r = 0.70, P = 0.0005) for 22 healthy volunteers. At 24:00 h and 03:00 h, sampling plasma at 30-s intervals provided no evidence for episodic secretion (in short pulses) of either melatonin or aMT6s.

P.L. Mcgeer

Papers

Metabolism of exogenous melatonin in schizophrenic and non-schizophrenic volunteers.