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

Ali Iranmanesh, Steve South, Ay Yin Liem, David Clemmons, Michael O. Thorner, Arthur Weltman, Johannes D Veldhuis

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-71
Number of pages13
JournalEuropean Journal of Endocrinology
Volume139
Issue number1
DOIs
StatePublished - Jul 1998
Externally publishedYes

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Growth Hormone-Releasing Hormone
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor I
Testosterone
Adipose Tissue
Serum
Obesity
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Adiposity
Periodicity
Luminescence
Body Composition
Somatostatin
Half-Life
Estradiol
Body Mass Index
Insulin
Therapeutics

ASJC Scopus subject areas

  • Endocrinology

Cite this

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. / Iranmanesh, Ali; South, Steve; Liem, Ay Yin; Clemmons, David; Thorner, Michael O.; Weltman, Arthur; Veldhuis, Johannes D.

In: European Journal of Endocrinology, Vol. 139, No. 1, 07.1998, p. 59-71.

Research output: Contribution to journalArticle

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abstract = "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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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

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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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