Circadian rhythm of free melatonin in human plasma.

The appearance of melatonin in saliva in concentrations up to 70% lower than those in blood has led to the suggestion that melatonin is bound to plasma protein and that saliva levels reflect the circulating free hormone. To test this directly, melatonin was measured in human plasma from 10 subjects after ultrafiltration through Centrifree micropartition tubes and compared to saliva melatonin levels in samples collected simultaneously. Melatonin was detected in the protein-free fraction and increased throughout the night in parallel with the saliva melatonin level. Peak concentrations ranged from 45-200 pmol/L (mean +/- SEM, 106 +/- 17 pmol/L) and averaged 23% of the total melatonin level. Across all samples, the correlation between the saliva levels and the free hormone levels was significant (r = 0.84; P < 0.05). These results provide the first direct evidence that endogenous melatonin is bound to plasma proteins and that saliva melatonin generally reflects the levels of this binding.

[1]  D. Dawson,et al.  Salivary Melatonin as a Circadian Phase Marker: Validation and Comparison to Plasma Melatonin , 1997, Journal of biological rhythms.

[2]  F. Lévi,et al.  Melatonin high-affinity binding to alpha-1-acid glycoprotein in human serum. , 1997, Pharmacology.

[3]  D. Kennaway,et al.  Characterization or the chicken brain melatonin‐binding protein using iodinated and triturated ligands , 1994, Journal of pineal research.

[4]  G. Vaughan.  New sensitive serum melatonin radioimmunoassay employing the Kennaway G280 antibody: Syrian hamster morning adrenergic response , 1993, Journal of pineal research.

[5]  M. Carrai,et al.  The effect of ageing on plasma albumin and plasma protein binding of diazepam, salicylic acid and digitoxin in healthy subjects and patients with renal impairment. , 1992, British journal of clinical pharmacology.

[6]  C. Mendel.  The free hormone hypothesis: a physiologically based mathematical model. , 1989, Endocrine reviews.

[7]  M. Schemper,et al.  Alterations in nocturnal serum melatonin levels in humans with growth and aging. , 1988, The Journal of clinical endocrinology and metabolism.

[8]  O. Vakkuri.  Diurnal rhythm of melatonin in human saliva. , 1985, Acta physiologica Scandinavica.

[9]  P. Routledge,et al.  The effects of age and smoking on the plasma protein binding of lignocaine and diazepam. , 1985, British journal of clinical pharmacology.

[10]  D. Kennaway,et al.  Effect of melatonin feeding on serum prolactin and gonadotropin levels and the onset of seasonal estrous cyclicity in sheep. , 1982, Endocrinology.

[11]  W. Pardridge,et al.  Transport of Albumin‐bound Melatonin Through the Blood‐Brain Barrier , 1980, Journal of neurochemistry.

[12]  S. Koslow,et al.  Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs. , 1976, The Journal of clinical endocrinology and metabolism.

[13]  E. Sellers,et al.  Drug therapy. Binding of drugs to serum albumin (second of two parts). , 1976, The New England journal of medicine.

[14]  E. Sellers,et al.  Binding of Drugs to Serum Albumin , 1976 .

[15]  R. Wurtman,et al.  Binding of melatonin to human and rat plasma proteins. , 1972, Endocrinology.