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Effect of Puberty on the Relationship between Circulating Leptin and Body Composition¹

Department of Pediatrics, Columbia University College of Physicians and Surgeons (M.B.H., M.R., R.L.L., L.S.L.), New York, New York 10032; Body Composition Unit, St. Luke’s/Roosevelt Hospital Center (J.W., B.F., R.N.P.) New York, New York 10019; and Amgen Inc. (M.N.), Thousand Oaks, California 91320-1789

Address correspondence and requests for reprints to: Michael Rosenbaum, M.D., Division of Molecular Genetics, Russ Berrie Medical Science Pavilion and Naomi Berrie Diabetes Center, 1150 St. Nicholas Avenue, New York, New York 10032. E-mail: mr475{at}columbia.edu

Circulating concentrations of leptin are better correlated with absolute amounts of adipose tissue [fat mass (FM)] than with relative body fatness (body mass index or percent body fat). There is a clear sexual dimorphism in circulating concentrations of leptin (females > males) at birth and in adulthood. However, whether such dimorphism is present in the interval between these periods of development remains controversial. We examined body composition and clinical (Tanner stage) and endocrine (pituitary-gonadal axis hormones) aspects of sexual maturation in relationship to circulating concentrations of leptin in 102 children (53 males and 49 females, 6–19 yr of age) to evaluate the relationship between circulating leptin concentrations and body composition before and during puberty.

Pubertal stage was assigned by physical examination (Tanner staging) and also assessed by measurement of plasma estradiol, testosterone, and pituitary gonadotropins. Body composition was determined by dual-energy x-ray absorptiometry and by anthropometry. Circulating concentrations of leptin in the postabsorptive state were determined by a solid-phase sandwich enzyme immunoassay. The effect of gender on the relationship between circulating leptin concentrations and FM was determined by ANOVA at each Tanner stage. Stepwise multiple linear regression analyses, including circulating concentrations of pituitary-gonadal axis hormones, and FM were performed, by gender, to determine whether the relationship between circulating concentrations of leptin and FM changes during puberty.

Plasma leptin concentrations were significantly correlated with FM at all Tanner 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 concentrations, normalized to FM, were significantly greater in females at Tanner 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. These significant gender and maturational differences were confirmed by demonstrating that the regression equation relating circulating leptin concentrations to FM in females and males at Tanner stages IV and V were significantly 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 concentrations 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 correlates of circulating concentrations of leptin normalized to FM in males when considered as a group over all pubertal stages. The inclusion in multivariate regression analyses of circulating concentrations of testosterone and estradiol, FM, fat-free mass, and gender did not eliminate a significant gender-effect (P < 0.05) on circulating concentrations of leptin at Tanner stages IV and V.

The circulating concentration of leptin, normalized to FM, declines significantly in males and rises significantly in females late in puberty to produce a late-pubertal/adult sexual dimorphism. These studies confirm a potent role for gonadal steroids as mediators of this sexual dimorphism in circulating concentrations of leptin. The persistence of a significant gender-effect on circulating leptin concentrations at Tanner stages IV and V, even when the regression equation includes body composition and circulating concentrations 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 additional X or Y- chromosome-linked gene effects that produce an increasing sexual dimorphism of circulating leptin concentrations later in puberty.

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