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.
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.
Veldhuis
J D
JD
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville.
Johnson
M L
ML
Faunt
L M
LM
Mercado
M
M
Baumann
G
G
D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D003198:Computer Simulation; D013006:Growth Hormone / Q000097:blood* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D012636:Secretory Rate
D002352:Carrier Proteins; D013006:Growth Hormone; C051815:somatotropin-binding protein