TY - JOUR
T1 - 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
T2 - Modeling analysis and clinical applications
AU - Veldhuis, Johannes D.
AU - Johnson, Michael L.
AU - Faunt, Lindsay M.
AU - Mercado, Moises
AU - Baumann, Gerhard
PY - 1993/2
Y1 - 1993/2
N2 - 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 or 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. 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.
AB - 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 or 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. 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.
KW - Diabetes mellitus
KW - Growth hormone
KW - Laron dwarfism
KW - Obesity
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U2 - 10.1172/JCI116243
DO - 10.1172/JCI116243
M3 - Article
C2 - 8432866
AN - SCOPUS:0027473686
SN - 0021-9738
VL - 91
SP - 629
EP - 641
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
ER -