6-Hydroxymelatonin sulfate excretion in human puberty.

We investigated the relationship of urinary excretion rate of 6-hydroxymelatonin sulfate (SM), the main metabolite of melatonin, with pubertal development and determined the day to day variability of SM excretion. Healthy subjects 4-31 years old completed one or multiple timed overnight urine collections. SM excretion rate per body size was significantly higher in 99 prepubertal subjects (35.5 +/- 2.3 ng/h/kg and 0.97 +/- 0.06 microgram/hr/m2) than in 86 pubertal subjects (18.1 +/- 1.1 ng/hr/kg and 0.61 +/- 0.03 microgram/hr/m2) or in 29 adults (15.0 +/- 1.5 ng/hr/kg and 0.59 +/- 0.06 microgram/hr/m2); no significant difference was present in pubertal stages 2 to 5. Among the prepubertal children, SM excretion rate in mid childhood was significantly higher than in late childhood. The variability of SM and creatinine excretion examined in 52 children, adolescents and adults with three or four collections was defined as the mean of the 52 coefficients of variation for the multiple measures in each subject. The variability of total nocturnal SM (25.9 +/- 2.6%) was similar to that of total creatinine (21.7 +/- 2.3%) and neither was significantly correlated with the variability in start time or duration of urine collection. The results suggest that, relative to body size, melatonin secretion rate is higher in mid childhood, decreases during late childhood, and remains stable from pubertal stage 2 to adulthood. The decline in melatonin secretion rate occurs during the developmental phase of disinhibition of the gonadotropin releasing hormone pulse generator. Hence, we infer that melatonin may be a suppressive factor of puberty during childhood. The substantial individual variability observed for SM excretion calls for caution in using single urine collections in longitudinal studies or in studies of drug responses.