Effect of puberty on the relationship between circulating leptin and body composition

Circulating concentrations of leptin are better correlated with absolute am ounts of adipose tissue [fat mass (FM)] than with relative body fatness (bo dy mass index or percent body fat). There is a clear sexual dimorphism in c irculating concentrations of leptin (females > males) at birth and in adult hood. However, whether such dimorphism is present in the interval between t hese periods of development remains controversial. We examined body composi tion and clinical (Tanner stage) and endocrine (pituitary-gonadal axis horm ones) aspects of sexual maturation in relationship to circulating concentra tions of leptin in 102 children (53 males and 49 females, 6-19 yr of age) t o evaluate the relationship between circulating leptin concentrations and b ody composition before and during puberty. Pubertal stage was assigned by physical examination (Tanner staging) and al so assessed by measurement of plasma estradiol, testosterone, and pituitary gonadotropins. Body composition was determined by dual-energy x-ray absorp tiometry and by anthropometry. Circulating concentrations of leptin in the postabsorptive state were determined by a solid-phase sandwich enzyme immun oassay. The effect of gender on the relationship between circulating leptin concentrations and FM was determined by ANOVA at each Tanner stage. Stepwi se multiple linear regression analyses, including circulating concentration s of pituitary-gonadal axis hormones, and FM were performed, by gender, to determine whether the relationship between circulating concentrations of le ptin and FM. changes during puberty. Plasma leptin concentrations were significantly correlated with FM at all T anner stages in males and females. Plasma leptin concentrations, normalized to FM, were significantly higher in females than males at Tanner stages IV and V but not at earlier stages of pubertal development. Plasma leptin con centrations, normalized to FM, were significantly greater in females at Tan ner stage V compared with females at Tanner stage I and significantly lower in males at Tanner stage IV and V compared with males at Tanner stage I. T hese significant gender and maturational differences were confirmed by demo nstrating that the regression equation relating circulating leptin concentr ations to FM in females and males at Tanner stages TV and V were significan tly different (predicted lower leptin concentrations in males than females with identical body composition) and that the regression equations relating circulating concentrations of leptin to FM in each gender before puberty ( Tanner stage I) were significantly different (predicted higher plasma conce ntrations of leptin in prepubertal males and lower leptin concentrations in prepubertal females) than the same regression equations in later puberty. Circulating concentrations of testosterone were significant negative correl ates of circulating concentrations of leptin normalized to FM: in males whe n considered as a group over all pubertal stages. The inclusion in multivar iate regression analyses of circulating concentrations of testosterone and estradiol, FM, fat-free mass, and gender did not eliminate a significant ge nder-effect (P < 0.05) on circulating concentrations of leptin at Tanner st ages IV and V. The circulating concentration of leptin, normalized to FM, declines signifi cantly in males and rises significantly in females late in puberty to produ ce a late-pubertal/adult sexual dimorphism. These studies confirm a potent role for gonadal steroids as mediators of this sexual dimorphism in circula ting concentrations of leptin. The persistence of a significant gender-effe ct on circulating leptin concentrations at Tanner stages IV and V, even whe n the regression equation includes body composition and circulating concent rations of gonadal steroids, however, suggests that this sexual dimorphism also reflects the direct or interactive effects of either other sex-related metabolic variables (such as insulin, GH, or body fat distribution) or add itional X or Y chromosome-linked gene effects that produce an increasing se xual dimorphism of circulating leptin concentrations later in puberty.