A twin study for serum leptin, soluble leptin receptor, and free insulin-like growth factor-I in pubertal females

Context: Leptin and IGF-I are two peripheral metabolic signals linking body energy status to hypothalamus GnRH generator and involved in the pubertal development and metabolic disorders. The changes of their biological activity through puberty and the genetic basis are not clear. Objective: To determine the genetic and environmental influences to the variations of basal leptin, soluble leptin receptor (SOB-R), free leptin index (FLI), and free IGF-I levels in pubertal females. Design: A twin study was performed in 2003. Setting: Participants were recruited from the Qingdao Twin Registry, a school-based registry. Participants: A total of 360 twin girls aged 6 - 18 yr were enrolled, consisting of 132 pairs of monozygotic and 48 pairs of dizygotic twins. Interventions: Anthropometric and sexual characteristics were examined. Serum total leptin and free IGF-I were measured by immunoradiometric assay, and SOB-R was measured by ELISA. Main Outcome Measure: Estimates of genetic and environmental components of variance were based on the theory of normal maximum likelihood in Mx package, a computer program specifically designed for the analysis of twin and family data. Results: Serum leptin concentrations increased persistently throughout puberty, especially from Tanner stage III to Tanner stage IV ( P <0.05), which in consistent with the increase of percentage of body fat. However, SOB-R decreased significantly from Tanner stage I to Tanner stage II ( P < 0.05), which results in a continuous rise of FLI ( ratio of leptin to SOB-R), especially from Tanner stage I to Tanner stage II ( P < 0.05). Serum free IGF-I increased dramatically from Tanner stage I to II and declined since then. Results of correlation analysis suggest that FLI predicts the pubertal growth and sexual maturation more effectively, whereas leptin sensitively reflects the fat mass of body composition. Quantitative genetic model fittings showed that SOB-R and free IGF-I have higher heritability ( 0.62 - 0.77, 0.54 - 0.66) and leptin and FLI have lower heritability (0.38 - 0.48, 0.44 - 0.55). Conclusions: Fast increase of FLI and free IGF-I from Tanner stage I to II might be involved in the onset of puberty and the onset of thelarche. The peak of free IGF-I in Tanner stage II might be presumed as an indicator of the peak of pubertal growth spurt in females, and the significant rise of leptin along with percentage of body fat from Tanner stage III to IV might be as a predictor of the forthcoming menarche. Our results stress the importance of research into the genetic regulation on the endocrine regulators involved in the pubertal development and metabolic disorders, including pubertal obesity and diabetes.