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Leptin Binding Activity Changes with Age: The Link between Leptin and Puberty¹

The Division of Clinical Sciences (N.D.Q., S.K.J., S.A.S., R.J.M.) and School of Health and Related Research (S.W.), Sheffield University; Biomedical Research Centre (N.D.Q., R.F.S., A.I.F.B.), Sheffield Hallam University; Endocrine Science Group (P.E.C., M.S.G.), University of Manchester; and The Christie Hospital (S.S.), Manchester, United Kingdom; and INSERM Unite 344 (M.-C.P.-V.), Faculte de Medicine Necker, 75730 Paris Cedex 15, France

Address all correspondence and requests for reprints to: Dr. R. J. M. Ross, Department of Medicine/Clinical Sciences, Northern General Hospital, Sheffield S5 7AU, United Kingdom and Dr. P. E. Clayton, Royal Manchester Children’s Hospital, Pendlebury, Manchester M27 4HA, United Kingdom. E-mail R.J.Ross{at}Sheffield.ac.uk

The timing of the physical transition from child to adult is determined by a biological clock that switches off the pituitary gonadal axis during infancy until puberty. Body composition (and in particular, fat mass), through leptin, are critical signals to this clock. However, no direct relationship between leptin and puberty has been demonstrated. Leptin is bound in the circulation by a high-affinity binding protein, which has been identified as a soluble leptin receptor. We found circulating levels of leptin binding activity (LBA) to be low at birth, to be high in the prepubertal years, to fall through puberty, and then to remain stable during adult life. LBA correlated with pubertal status in both boys and girls. We postulate that the fall in LBA, associated with increasing age and puberty, reflects a reduction in expression of truncated leptin receptors, and leptin is then available to the full-length receptor, which transmits the biological signal for leptin. The high levels of LBA occur during the years when the pituitary gonadal axis is quiescent. Thus, the change in LBA could explain how leptin regulates puberty.

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