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.

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

doi:10.1172/jci116243

Cited by 91 publications

(44 citation statements)

References 46 publications

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“…This most likely reflects the inverse relationship between the metabolic clearance rate of GH and circulating GH concentrations (42). Alternatively, an increase in serum GH-binding protein levels (not measured here) during GHRH infusions could in principle prolong GH half-life (43).…”

Section: Discussionmentioning

confidence: 90%

Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men

Iranmanesh

South

Liem

et al. 1998

European Journal of Endocrinology

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We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 mg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRHdriven pulsatile GH secretion (in randomly ordered sessions) were quantitated by deconvolution analysis of 24-h (10-min sampling) serum GH concentration profiles measured in an ultrasensitive (threshold 0.005 mg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 Ϯ 0.1 basal vs 2.4 Ϯ 0.4 mg/l treatment; P ¼ 0.0001), total daily pulsatile GH production rate (21 Ϯ 9.5 vs 97 Ϯ 17 mg/l/day; P ¼ 0.01), GH secretory burst frequency (11 Ϯ 0.5 vs 17 Ϯ 0.3 events/day; P ¼ <0.01), and mass of GH released per burst (1.1 Ϯ 0.4 vs 5.9 Ϯ 1 mg/l; P < 0.01), as well as serum IGF-I (261 Ϯ 33 vs 436 Ϯ 37 mg/l; P ¼ 0.005), insulin (45 Ϯ 13 vs 79 Ϯ 17 mU/l; P ¼ 0.0002), and IGF binding protein (IGFBP)-3 (3320 Ϯ 107 vs 4320 Ϯ 114 mg/l; P ¼ 0.001) concentrations, while decreasing IGFBP-1 levels (16 Ϯ 1.2 vs 14 Ϯ 0.09 mg/l; P ¼ 0.02). Serum total testosterone and estradiol concentrations did not change. GHRH treatment also reduced the half-duration of GH secretory bursts, and increased the GH half-life. GHRH-stimulated 24-h serum GH concentrations and the mass of GH secreted per burst were correlated negatively with age (R[value]:P[value] ¼ ¹0.67:0.002 and ¹0.58:0.009 respectively), and percentage body fat (R:P ¼ ¹0.80:0.0001 and ¹0.65:0.005 respectively), but positively with serum testosterone concentrations (R:P ¼ þ 0.55:0.016 and þ 0.53:0.019 respectively). GHRHstimulated plasma IGF-I increments correlated negatively with age and body mass index, and positively with serum testosterone, but not with percentage body fat. Cosinor analysis disclosed persistent nyctohemeral rhythmicity of GH secretory burst mass (with significantly increased 24-h amplitude and mesor values) but unchanged acrophase during fixed pulsatile GHRH infusions, which suggests that both GHRH-and non-GHRH-dependent mechanisms can modulate the magnitude (but only non-GHRH mechanisms can modulate the timing) of somatotrope secretory activity differentially over a 24-h period.In summary, diminished GHRH action and/or non-GHRH-dependent mechanisms (e.g. somatostatin excess, putative endogenous growth hormone-releasing peptide deficiency etc.) probably underlie the hyposomatotropism of aging, (relative) obesity, and/or hypoandrogenemia. Preserved or increased tissue IGF-I responses to GHRH-stimulated GH secretion (albeit absolutely reduced, suggesting GHRH insensitivity in obesity) may distinguish the pathophysiology of adiposity-associated hyposomatotropism from that of healthy aging.

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Section: Discussionmentioning

confidence: 90%

Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men

Iranmanesh

South

Liem

et al. 1998

European Journal of Endocrinology

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“…Most studies of GH half-life describe elimination after GH infusion, finding a half-life of total GH of around 15 -20 min following mono-exponential decay curves (13,18,25,29). Alterations in GH levels induce minor changes in the half-life, suggesting saturation of elimination pathways at high concentrations (18,29).…”

Section: Discussionmentioning

confidence: 99%

Kinetics and secretion of placental growth hormone around parturition

Fuglsang¹,

Sandager²,

Møller³

et al. 2006

eur j endocrinol

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Objective: During pregnancy, placental growth hormone (PGH) is secreted into the maternal circulation, replacing pituitary GH. It is controversial whether PGH levels decline during vaginal birth. After placental expulsion, PGH is eliminated from the maternal blood. GH binding protein (GHBP) and body mass index (BMI) influence GH kinetics, but their impact on PGH kinetics is unknown. The present study was undertaken to define the kinetics of PGH during vaginal delivery and Caesarian section and to relate these kinetics to GHBP and BMI. Design: A short term, prospective cohort study. Methods: Twelve women had repeated blood samples drawn during vaginal delivery. From 26 women undergoing planned Caesarian delivery (CS) repeated blood samples were withdrawn before, during and after the CS, allowing PGH half-life determination. Results: During vaginal delivery, median PGH values did not change before expulsion of the placenta, although individual fluctuations were seen. Clearance of PGH from the maternal circulation was best described by a two-compartment model. The initial half-life of serum PGH was (mean^S.D.) 5.8^2.4 min, and the late half-life was (median) 87.0 min (range: 25.1 -679.6 min). The late halflife was correlated to the pre-gestational BMI (r ¼ 0.39, P ¼ 0.047), but not to the serum GHBP concentration. Conclusions: Serum PGH did not decrease significantly during vaginal delivery. Elimination of PGH fitted a two-compartment model, with an estimated initial half-life of 5.8 min. The late phase serum half-life of PGH was related to BMI, suggesting a role for maternal fat mass in PGH metabolism.European Journal of Endocrinology 154 449-457

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“…This mode of action appears to be especially important when the site of ligand production is distant from its target tissue, as is the case of growth hormone [19,114,115]. Thus, the extracellular domain of the growth hormone receptor is the serum growth hormone binding protein that functions to keep growth hormone in the blood for a longer period of time [115,116]. Some soluble receptors are able to associate with membrane-bound subunits to effect signal transduction (Fig.…”

Section: Mechanisms Of Soluble Receptor Actionmentioning

confidence: 99%