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.
J D Veldhuis, M L Johnson, L M Faunt, M Mercado, G Baumann
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The Pituitary | 2011 |
Current Topics in Developmental Biology
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Cancer and Development | 2011 |
Overtrained horses alter their resting pulsatile growth hormone secretion
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Growth Hormone & IGF Research | 2009 |
Yen & Jaffe's Reproductive Endocrinology
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Yen & Jaffe's Reproductive Endocrinology | 2009 |
Overtrained horses alter their resting pulsatile growth hormone secretion
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American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2009 |
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Endocrine reviews | 2008 |
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Expert Opinion on Drug Metabolism & Toxicology | 2008 |
PEGylation of somatropin (recombinant human growth hormone): Impact on its clearance in humans
R Webster, R Xie, E Didier, R Finn, J Finnessy, A Edgington, D Walker |
Xenobiotica | 2008 |
Determination of Free Growth Hormone
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The Journal of clinical endocrinology and metabolism | 2008 |
Aspects of placental growth hormone physiology
J Fuglsang, P Ovesen |
Growth Hormone & IGF Research | 2006 |
Physiology and pathophysiology of growth hormone-binding protein: Methodological and clinical aspects
S Fisker |
Growth Hormone & IGF Research | 2006 |
Kinetics and secretion of placental growth hormone around parturition
J Fuglsang, P Sandager, N Moller, S Fisker, H Orskov, P Ovesen |
European Journal of Endocrinology | 2006 |
In vitro bioassay as a predictor of in vivo response
R Barnard, KG Gurevich |
Theoretical biology & medical modelling | 2005 |
Growth hormone binding protein and maternal body mass index in relation to placental growth hormone and insulin requirements during pregnancy in type 1 diabetic women
J Fuglsang, FF Lauszus, S Fisker, A Flyvbjerg, P Ovesen |
Growth Hormone & IGF Research | 2005 |
Differential Impact of Simple Childhood Obesity on the Components of the Growth Hormone-Insulin-like Growth Factor (IGF)-IGF Binding Proteins Axis
MG Ballerini, MG Ropelato, HM Domené, P Pennisi, JJ Heinrich, HG Jasper |
Journal of Pediatric Endocrinology and Metabolism | 2004 |
Laboratory measurement of growth hormone
V Popii, G Baumann |
Clinica Chimica Acta | 2004 |
Clinical pharmacological aspects of growth hormone administration
T Laursen |
Growth Hormone & IGF Research | 2004 |
A Truncated Isoform of c-Mpl with an Essential C-terminal Peptide Targets the Full-length Receptor for Degradation
J Coers, C Ranft, RC Skoda |
The Journal of biological chemistry | 2004 |
Human GH pulsatility: An ensemble property regulated by age and gender
JD Veldhuis, CY Bowers |
Journal of Endocrinological Investigation | 2003 |
Sex-Steroid Modulation of Growth Hormone (GH) Secretory Control: Three-Peptide Ensemble Regulation Under Dual Feedback Restraint by GH and IGF-I
JD Veldhuis, CY Bowers |
Endocrine | 2003 |
Neuroendocrine facets of human puberty
JD Veldhuis |
Neurobiology of Aging | 2003 |
Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men
JD Veldhuis, M Bidlingmaier, SM Anderson, WS Evans, Z Wu, CJ Strasburger |
The Journal of clinical endocrinology and metabolism | 2002 |
Pharmacokinetics and acute lipolytic actions of growth hormone
TK Hansen |
Growth Hormone & IGF Research | 2002 |
Altered GH Elimination Kinetics in Type 1 Diabetes Mellitus Can Explain the Elevation in Circulating Levels: Bicompartmental Approach
PF Catalina, MA Andrade, RV García-Mayor, F Mallo |
The Journal of clinical endocrinology and metabolism | 2002 |
Growth Hormone Binding Protein 2001
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Journal of Pediatric Endocrinology and Metabolism | 2001 |
Growth hormone treatment in adults:Is there a true gender difference?
FL Conceição, S Fisker, N Vahl, TK Hansen, JO Jørgensen, JS Christiansen |
Growth Hormone & IGF Research | 2001 |
Estimation of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach
JG Langendonk, JD Veldhuis, J Burggraaf, RC Schoemaker, AF Cohen, AE Meinders, H Pijl |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2001 |
Quantitative determination of ceramide using diglyceride kinase
DK Perry, A Bielawska, YA Hannun |
Methods in enzymology | 2000 |
Explicating hypergonadotropism in postmenopausal women: a statistical model
DM Keenan, JD Veldhuis |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2000 |
Impact of acute exercise intensity on pulsatile growth hormone release in men
CJ Pritzlaff, L Wideman, JY Weltman, RD Abbott, ME Gutgesell, ML Hartman, JD Veldhuis, A Weltman |
Journal of applied physiology | 1999 |
Influence of obesity and body fat distribution on growth hormone kinetics in humans
JG Langendonk, AE Meinders, J Burggraaf, M Frölich, CA Roelen, RC Schoemaker, AF Cohen, H Pijl |
American journal of physiology. Endocrinology and metabolism | 1999 |
Alternative Processing of Growth Hormone Receptor Transcripts*
A Edens, F Talamantes |
Endocrine reviews | 1998 |
Evaluation of growth hormone assays using ratio plots
M Andersen, PH Petersen, O Blaabjerg, J Hangaard, C Hagen |
Clinical chemistry | 1998 |
Granulocyte colony-stimulating factor receptor expression on human transitional cell carcinoma of the bladder
M Tachibana, A Miyakawa, A Uchida, M Murai, K Eguchi, K Nakamura, A Kubo, JI Hata |
British Journal of Cancer | 1997 |
Growth Factors and Cytokines in Health and Disease
P Martin, J McCluskey, P Mallucci, S Nodder |
Growth Factors and Cytokines in Health and Disease | 1997 |
Growth hormone-binding protein: biological significance
MC Postel-Vinay |
Acta Paediatrica | 1996 |
Growth hormone binding protein and free growth hormone in chronic renal failure
G Baumann |
Pediatric Nephrology | 1996 |
Methods in Neurosciences
V Rybin, HM Han, SF Steinberg |
Methods in Neurosciences | 1996 |
Facilitation of the Growth Promoting Effect of Growth Hormone (GH) by an Antibody to Methionyl-GH
BK Suh, ΕV Jorgensen, AW Root |
Journal of Pediatric Endocrinology and Metabolism | 1995 |
Metabolic clearance of recombinant human growth hormone in health and chronic renal failure
D Haffner, F Schaefer, J Girard, E Ritz, O Mehls |
Journal of Clinical Investigation | 1994 |
Metabolic effects of growth hormone administered subcutaneously once or twice daily to growth hormone deficient adults
T Laursen, JO Jergensen, JS Chrlstiansen |
Clinical Endocrinology | 1994 |
Analytical methods for evaluating episodic secretory activity within neuroendocrine axes
JD Veldhuis, ML Johnson |
Neuroscience & Biobehavioral Reviews | 1994 |
Heterogeneity of circulating growth hormone
G Baumann, M Shaw, K Amburn, T Jan, N Davila, M Mercado, M Stolar, MC John |
Nuclear Medicine and Biology | 1994 |
Gene targeting and generation of mutant mice for studies of cell-extracellular matrix interactions
KL Philpott, JL Viney, G Kay, S Rastan, EM Gardiner, S Chae, AC Hayday, MJ Owen |
Methods in enzymology | 1994 |
Circulating growth hormone binding proteins
G Baumann, MA Shaw, K Amburn |
Journal of Endocrinological Investigation | 1994 |