Published in Volume
91, Issue 2 (February 1993)
J Clin Invest. 1993;91(2):629–641.
doi:10.1172/JCI116243.
Copyright ©
1993, The American Society for
Clinical Investigation.
Research Article
Amended: Correction (May 1993)
|
Correction (August 1993)
Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. Modeling analysis and clinical applications.
J D Veldhuis, M L Johnson, L M Faunt, M Mercado and G Baumann
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville.
Published February 1993
The discovery of a specific high-affinity growth hormone (GH) binding protein (GH-BP) in plasma adds complexity to the dynamics of GH secretion and clearance. Intuitive predictions are that such a protein would damp sharp oscillations in GH concentrations otherwise caused by bursts of GH secretion into the blood volume, prolong the apparent half-life of circulating GH, and contribute a reservoir function. To test these implicit considerations, we formulated an explicit mathematical model of pulsatile GH secretion and clearance in the presence of absence of a specific high-affinity GH-BP. Simulation experiments revealed that the pulsatile mode of physiological GH secretion creates a highly dynamic (nonequilibrium) system, in which the half-life of free GH, its instantaneous secretion rate, and the GH-BP affinity and capacity all contribute to defining momentary levels of free, bound, and total GH, the percentage of GH bound to protein, and the percentage occupancy of GH-BP [corrected]. In contrast, the amount of free GH at equilibrium is specified only by the GH distribution volume and secretion rate and the half-life of free hormone. We conclude that the in vivo dynamics of GH secretion, trapping, and clearance from the circulation offer a variety of regulatory loci at which the time structure of free, bound, and total GH delivery to target tissues can be controlled physiologically.
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