Leptin Binding Activity Changes with Age: The Link between Leptin and Puberty1
N. D. Quinton,
R. F. Smith,
P. E. Clayton,
M. S. Gill,
S. Shalet,
S. K. Justice,
S. A. Simon,
S. Walters,
M.-C. Postel-Vinay,
A. I. F. Blakemore and
R. J. M. Ross
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 isdetermined
by a biological clock that switches off the pituitarygonadal axis
during infancy until puberty. Body composition(and in particular, fat
mass), through leptin, are criticalsignals to this clock. However, no
direct relationship betweenleptin and puberty has been demonstrated.
Leptin is bound inthe circulation by a high-affinity binding protein,
which hasbeen identified as a soluble leptin receptor. We found
circulatinglevels of leptin binding activity (LBA) to be low at birth,
tobe high in the prepubertal years, to fall through puberty, andthen
to remain stable during adult life. LBA correlated withpubertal status
in both boys and girls. We postulate that thefall in LBA, associated
with increasing age and puberty, reflectsa reduction in expression of
truncated leptin receptors, andleptin is then available to the
full-length receptor, whichtransmits the biological signal for leptin.
The high levelsof LBA occur during the years when the pituitary
gonadal axisis quiescent. Thus, the change in LBA could explain how
leptinregulates puberty.
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