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

Johannes D. Veldhuis, Michael L. Johnson, Lindsay M. Faunt, Moises Mercado, Gerhard Baumann

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)629-641
Number of pages13
JournalJournal of Clinical Investigation
Volume91
Issue number2
DOIs
StatePublished - Feb 1993

Keywords

  • Diabetes mellitus
  • Growth hormone
  • Laron dwarfism
  • Obesity

ASJC Scopus subject areas

  • Medicine(all)

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