Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Vance, Mary Lee; Kaiser, Donald L.; Evans, William S.; Furlanetto, Richard W.; Vale, Wylie; Rivier, Jean; Thorner, Michael O.

doi:10.1172/jci111864

Cited by 181 publications

(83 citation statements)

References 23 publications

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“…Such diurnal variations during an unchanging GHRH stimulus suggest to us (but do not prove) concomitant 24-h non-uniformity in the release of somatostatin and/or co-secretagogues of GH. These considerations would also explain ongoing pulsatile GH release during continuous GHRH infusions (40). Since the amplitude and mesor (but not the acrophase) of the 24-h rhythm in GH secretory burst mass increased (by 2.5-and 3.5-fold respectively) during GHRH infusion, we infer that the magnitude but not the timing of daynight GH rhythmicity is modulated by GHRH.…”

Section: Discussionmentioning

confidence: 82%

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: 82%

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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“…IGF-I administration in this syndrome diminishes GH secretion, indicating that feedback can be restored (28). The amplified GH secretion is likely mediated by increased hypothalamic GHRH output, while somatostatin release is not affected in view of the unchanged GH pulsatility (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 89%

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

et al. 2007

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Objective: STAT5b is a component of the GH signaling pathway. Recently, we described a 31-year-old male patient (height, K5.9 SDS) with a novel homozygous inactivating mutation in the STAT5b gene. The purpose of this study is to describe the phenotype in detail, including GH secretion and immunological function. In addition, we report four family members of this patient, all heterozygous carriers of the mutation. Design and methods: Twenty-four hour GH and prolactin secretion characteristics were assessed by blood sampling at 10-min intervals. An IGF-I generation test was performed. Monocyte function was tested by stimulation of whole blood with lipopolysaccharide (LPS) in the presence or absence of Interferon-g (IFN-g). In addition, T cell function was determined by measuring proliferative responses of peripheral blood mononuclear cells (PBMC) after stimulation by various polyclonal activators and Interleukin-2 (IL-2). Clinical and biochemical characteristics were determined in the carriers of the mutation. Results: GH secretory parameters were comparable with that of healthy male controls (mean fat percentage 25), but likely increased in relation to the patient's 40% body fat. The regularity of GH secretion was diminished. Prolactin secretion was increased by sixfold. The IGF-I generation test showed a small increase in IGF-I and IGF-binding protein-3 on lower GH doses and an increase in IGF-I to K2.4 SDS on the highest dose of GH. In vitro, IL-12p40, IL 10, and tumour necrosis factor-a (TNF-a) production rates by PBMC increased to values within the normal range upon stimulation of LPS. Heterozygous carriers of the mutation did not show abnormalities, although the height of the males was below the normal range. Conclusions: This report shows that GH and prolactin secretion were increased in this patient homozygous for a new STAT5b mutation. Although STAT5b plays a role in signaling within immune cells, clinical immunodeficiency is not an obligatory phenomenon of STAT5b deficiency per se. Heterozygous carriers of a STAT5b mutation show no signs of GH insensitivity. 156 155-165 European Journal of Endocrinology

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“…Measurement of GHRH levels during dynamic tests other than in the basal state has no diagnostic utility, but it may give some insight into the inter-relationship between GHRH and GH secretion in man. Vance et al (1985) found a significant correlation between GHRH and GH levels during a 24 h profile study in a patient with the ectopic GHRH syndrome. We also detected a significant correlation between the two hormones in two different patients with the ectopic GHRH syndrome (Losa et al, 1993), even though the study period was much shorter (8 h).…”

Section: Laboratory Findingsmentioning

confidence: 79%

“…Analysis of GH pulsatility and circadian rhythm has been performed rarely in patients with ectopic GHRH syndrome. When frequent blood sampling was performed, a clear pulsatility of GH levels was detected (Wilson et al, 1984;Vance et al, 1985), whereas lack of pulsatility was reported in two other patients, although both studies had a less frequent pattern of blood sampling (Ch'ng et al, 1985;Barkan et al, 1986). Loss of circadian rhythmicity was suggested in three patients who did not show any nocturnal GH surge (Ch'ng et al, 1985;Vance et al, 1985;Yamasaki et al, 1988b).…”

Section: Laboratory Findingsmentioning

confidence: 99%

Pathophysiology and clinical aspects of the ectopic GH‐releasing hormone syndrome

Losa¹,

Werder²

1997

Clinical Endocrinology

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Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.

Cited by 181 publications

References 23 publications

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

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

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

Pathophysiology and clinical aspects of the ectopic GH‐releasing hormone syndrome

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