Mice convert melatonin to 6-sulphatoxymelatonin.
The principal objective of this study was to establish whether mice can convert melatonin to 6-sulphatoxymelatonin (aMT6s). Precision-cut liver slices from C3H/He, C57BL/6, and BALB/c mice were incubated with melatonin, and the concentration of aMT6s in the culture media was determined using a sensitive and specific radioimmunoassay procedure. All three strains of mice generated aMT6s in a time-dependent manner; no significant strain differences were observed. When samples of the media were treated with sulphatase prior to analysis, aMT6s was not detectable. In contrast, similar treatment with beta-glucuronidase had no effect. 6-Sulphatoxymelatonin was present in the urine of both control and melatonin-treated C3H/He and C57BL6 mice. Treatment with melatonin led to a dramatic rise in the urinary levels of aMT6s in both mouse strains. Pre-treatment of the urines with sulphatase, but not beta-glucuronidase, markedly decreased the levels of aMT6s. Finally, in both strains urinary excretion of aMT6s displayed diurnal rhythmicity, peak excretion occurring during the dark hours. It may be inferred that: (a) mice can convert melatonin to aMT6s, both in vivo and in vitro, and (b) mice generate aMT6s in a rhythmic manner. Finally, the present studies confirm that determination of aMT6s rhythms in mice could provide an alternative, non-invasive, approach for assessing circadian clock function.
School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Debra J
DJ
Skene
Sarah E
SE
Timbers
Benita
B
Middleton
Judie
J
English
Caroline
C
Kopp
Irene
I
Tobler
Costas
C
Ioannides
D000818:Animals; D015415:Biomarkers / Q000652:urine; D002940:Circadian Rhythm / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism* / Q000652:urine; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology
D015415:Biomarkers; C054513:6-sulfatoxymelatonin; D008550:Melatonin