PLASMA LEPTIN LEVELS IN HEALTHY-CHILDREN AND ADOLESCENTS - DEPENDENCEON BODY-MASS INDEX, BODY-FAT MASS, GENDER, PUBERTAL STAGE, AND TESTOSTERONE

Leptin, the product of the ob gene, is thought to play a key role in t he regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feed back loops. Because childhood and puberty are periods of major metabol ic and endocrine changes, leptin levels and various hormonal parameter s were investigated in a large cohort of healthy children and adolesce nts (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a spe cific and sensitive RIA was developed that allowed the accurate measur ement of low leptin levels in young lean children. With this assay, le ptin proved to be a comparatively stable protein under common conditio ns of blood sampling and storage. Leptin levels increased in girls wit h age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0. 0001). An analysis according to pubertal stage showed a steady increas e in girls between 2.51 mu g/L (median) at Tanner stage 1 to 6.24 mu g /L at Tanner stage 5. In boys, leptin levels were highest at Tanner st age 2 (2.19 mu g/L) and declined thereafter to 0.71 mu g/L at Tanner s tage 5. A strong exponential relationship was observed for leptin leve ls with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This re lationship was similar between boys and girls at Tanner stages 1 and 2 . In boys, there was a significant decline of leptin at a given BMI wi th further progression of puberty that was much less pronounced in gir ls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty a nd in adolescents. In boys, but not in girls, there was an inverse cor relation with testosterone concentrations (r = -0.43, P < 0.0001), whi ch explained 10.5% of the variation of leptin levels in a multiple reg ression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = ae((b*BMI)) and stratifying ranges according to gen der and pubertal stage. In conclusion, these data suggest that 1) plas ma leptin levels increase in girls and decrease in boys after Tanner s tage 2 as the pubertal development proceeds; 2) they show a significan t gender difference especially in late puberty and adolescence; even a fter adjustment for BMI or percent body fat; 3) the lower levels in ma les may be explained at least in part by a suppressive effect of andro gens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.