6-HYDROXYMELATONIN SULFATE EXCRETION IN HUMAN PUBERTY

We investigated the relationship of urinary excretion rate of 6-hydrox ymelatonin sulfate (SM), the main metabolite of melatonin, with pubert al development and determined the day to day variability of SM excreti on. Healthy subjects 4-31 years old completed one or multiple timed ov ernight urine collections. SM excretion rate per body size was signifi cantly higher in 99 prepubertal subjects (35.5 +/- 2.3 ng/h/kg and 0.9 7 +/- 0.06 mu g/hr/m(2)) than in 86 pubertal subjects (18.1 +/- 1.1 ng /hr/kg and 0.61 +/- 0.03 mu g/hr/m(2)) or in 29 adults (15.0 +/- 1.5 n g/hr/kg and 0.59 +/- 0.06 mu g/hr/m(2)); 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 wa s defined as the mean of the 52 coefficients of variation for the mult iple 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 star t time or duration of urine collection. The results suggest that, rela tive to body size, melatonin secretion rate is higher in mid childhood , decreases during late childhood, and remains stable from pubertal st age 2 to adulthood. The decline in melatonin secretion rate occurs dur ing the developmental phase of disinhibition of the gonadotropin relea sing hormone pulse generator. Hence, we infer that melatonin may be a suppressive factor of puberty during childhood. The substantial indivi dual variability observed for SM excretion calls for caution in using single urine collections in longitudinal studies or in studies of drug responses.