TY - JOUR
T1 - Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotropic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men
AU - Iranmanesh, Ali
AU - South, Steve
AU - Liem, Ay Yin
AU - Clemmons, David
AU - Thorner, Michael O.
AU - Weltman, Arthur
AU - Veldhuis, Johannes D.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/7
Y1 - 1998/7
N2 - 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 μg/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 GHRH-driven 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 μg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 ± 0.1 basal vs 2.4 ± 0.4 μg/l treatment; P= 0.0001), total daily pulsatile GH production rate (21 ± 9.5 vs 97 ± 17 μg/l/day; P = 0.01), GH secretory burst frequency (11 ± 0.5 vs 17 ± 0.3 events/day; P= <0.01), and mass of GH released per burst (1.1 ± 0.4 vs 5.9 ± 1 μg/l; P<0.01), as well as serum IGF-I (261 ± 33 vs 436 ± 37 μg/l: P=0.005), insulin (45 ± 13 vs 79 ± 17 mU/l; P=0.0002), and IGF binding protein (IGFBP)-3 (3320 ± 107 vs 4320 ± 114 μg/l; P=0.001) concentrations, while decreasing IGFBP-1 levels (16 ± 1.2 vs 14 ± 0.09 μg/l; P= 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] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P= -0.80:0.0001 and -0.65:0.005 respectively), but positively with serum testosterone concentrations (R:P= +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated 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.
AB - 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 μg/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 GHRH-driven 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 μg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 ± 0.1 basal vs 2.4 ± 0.4 μg/l treatment; P= 0.0001), total daily pulsatile GH production rate (21 ± 9.5 vs 97 ± 17 μg/l/day; P = 0.01), GH secretory burst frequency (11 ± 0.5 vs 17 ± 0.3 events/day; P= <0.01), and mass of GH released per burst (1.1 ± 0.4 vs 5.9 ± 1 μg/l; P<0.01), as well as serum IGF-I (261 ± 33 vs 436 ± 37 μg/l: P=0.005), insulin (45 ± 13 vs 79 ± 17 mU/l; P=0.0002), and IGF binding protein (IGFBP)-3 (3320 ± 107 vs 4320 ± 114 μg/l; P=0.001) concentrations, while decreasing IGFBP-1 levels (16 ± 1.2 vs 14 ± 0.09 μg/l; P= 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] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P= -0.80:0.0001 and -0.65:0.005 respectively), but positively with serum testosterone concentrations (R:P= +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated 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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U2 - 10.1530/eje.0.1390059
DO - 10.1530/eje.0.1390059
M3 - Article
C2 - 9703380
AN - SCOPUS:0031856428
SN - 0804-4643
VL - 139
SP - 59
EP - 71
JO - European journal of endocrinology
JF - European journal of endocrinology
IS - 1
ER -