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Changes in Circulating Leptin, Leptin Receptor, and Gonadal Hormones from Infancy until Advanced Age in Humans

Cooperative Reproductive Science Research Center and Department of Physiology, Morehouse School of Medicine (D.R.M.), Atlanta, Georgia 30310; and Departments of Obstetrics and Gynecology (T.G., V.D.C.) and Pediatrics (A.O.K.J.), Texas Tech University Health Sciences Center, Amarillo, Texas 79106

Address all correspondence and requests for reprints to: David R. Mann, Ph.D., Cooperative Reproductive Science Research Center, Department of Physiology, 720 Westview Drive SW, Atlanta, Georgia 30310.

We determined developmental changes in circulating levels of the soluble leptin receptor (sOB-R), leptin, and gonadal hormones in human subjects. In both sexes the rise in leptin with age was associated with a decline in sOB-R, and age-related changes in both parameters preceded the pubertal rise in gonadal hormones. Leptin levels above 10 ng/ml were a strong predictor of sOB-R concentrations, but this predictive value decreased as leptin declined. In young subjects there were no gender differences in serum leptin, but boys had higher sOB-R levels. In adults neither leptin nor sOB-R changed with age, but serum leptin was higher and sOB-R was lower in women than men. There was a significant negative correlation between sOB-R and leptin in women, but not men. The data suggest that bioavailable leptin in the circulation may be increasing more rapidly during development than indicated by total leptin levels, and that these changes may serve as one of the signals to the central nervous system that metabolic conditions are adequate to support pubertal development. Furthermore, the study provides suggestive evidence that leptin regulates the secretion of its own binding protein, but it also appears that an additional gender-specific, leptin-independent, regulatory mechanism is functional before puberty.

This work was supported by NIH Grants HD-41749 and GM-08248 (to Morehouse School of Medicine).

Present address for V.D.C.: Diagnostic Systems Laboratories, Inc., Webster, Texas.

Abbreviations: BMI, Body mass index; sOB-R, soluble leptin receptor.

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