Acipimox enhances spontaneous growth hormone secretion in obese women

2004 ◽  
Vol 286 (4) ◽  
pp. R693-R698 ◽  
Author(s):  
Petra Kok ◽  
Madelon M. Buijs ◽  
Simon W. Kok ◽  
Inge H. A. P. van Ierssel ◽  
Marijke Frölich ◽  
...  

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 ± 1.0 kg/m2) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 ± 10 vs. lean controls: 201 ± 23 mU·lVd-1·24 h-1, P = 0.005, where lVd is liter of distribution volume). Acipimox considerably enhanced total (113 ± 50 vs. 66 ± 10 mU·lVd-1·24 h-1, P = 0.02) and pulsatile GH secretion (109 ± 49 vs. 62 ± 30 mU·lVd-1·24 h-1, P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

2009 ◽  
Vol 297 (2) ◽  
pp. R403-R411 ◽  
Author(s):  
E. de Graaf-Roelfsema ◽  
P. P. Veldhuis ◽  
H. A. Keizer ◽  
M. M. E. van Ginneken ◽  
K. G. van Dam ◽  
...  

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.


2018 ◽  
Vol 19 (10) ◽  
pp. 3067 ◽  
Author(s):  
Xinli Zhang ◽  
Jin-Kui Yang ◽  
Chen Chen

Significant growth hormone (GH) reductions have been reported in diabetic animal models with disturbed metabolic balance coinciding with GH deficiency. Therefore, enhanced GH secretion may have beneficial effects in controlling diabetes. Thus, we aim to investigate the effect of hexarelin, a synthetic GH secretagogue (GHS), on GH secretion in streptozotocin (STZ, 65 mg/kg)-induced diabetic rats. Daily hexarelin (100 μg/kg) treatment was performed for two weeks in four-week-long STZ-diabetic and vehicle control rats. Pulsatile GH secretion in STZ-rats was significantly reduced in total, pulsatile, basal, and mass of GH secretion per burst. In addition, impaired GH secretion was followed by an increase in fasting-level free fatty acids (FFAs) and a decrease in insulin-like growth factor 1 (IGF-1) compared to control rats. After hexarelin treatment, pulsatile GH secretion in STZ-rats was significantly increased in total, pulsatile, and basal, but not in the mass GH secretion per burst, compared to STZ-rats without hexarelin treatment. However, there was no significant elevation in GH secretion in the hexarelin-treated control group. In addition, hexarelin-treated STZ-rats showed a significant decrease in fasting level FFAs, whereas suppression of fasting level for IGF-1 was maintained. These results suggest that STZ-induced diabetic rats have impaired pulsatile GH secretion, causing increased FFAs and decreased IGF-1 levels in circulation. Hexarelin injections for two weeks is able to normalize impaired pulsatile GH secretion with normal fasting levels of FFAs, but fails to recover IGF-1 levels.


1999 ◽  
Vol 276 (5) ◽  
pp. R1351-R1358 ◽  
Author(s):  
N. Shah ◽  
W. S. Evans ◽  
J. D. Veldhuis

The neuroendocrine mechanisms by which estradiol drives growth hormone (GH) secretion in the human are poorly defined. Here we investigate estrogen’s specific regulation of the 24-h pulsatile, nyctohemeral, and entropic modes of GH secretion in healthy postmenopausal women. Volunteers ( n = 9) received randomly ordered placebo versus estradiol-17β (1 mg micronized steroid twice daily orally) treatment for 7–10 days and underwent blood sampling at 10-min intervals for 24 h to capture GH release profiles quantitated in a high-sensitivity chemiluminescence assay. Pulsatile GH secretion was appraised via deconvolution analysis, nyctohemeral GH rhythms by cosinor analysis, and the orderliness of GH release patterns via the approximate entropy statistic. Mean (±SE) 24-h serum GH concentrations approximately doubled on estrogen treatment (viz., from 0.31 ± 0.03 to 0.51 ± 0.07 μg/l; P = 0.033). Concomitantly, serum insulin-like growth factor-I (IGF-I), luteinizing hormone, and follicle-stimulating hormone concentrations fell, whereas thyroid-stimulating hormone and prolactin levels rose ( P < 0.01). The specific neuroendocrine action of estradiol included 1) a twofold amplified mass of GH secreted per burst, with no significant changes in basal GH release, half-life, pulse frequency, or duration; 2) an augmented amplitude and mesor of the 24-h rhythm in GH release, with no alteration in acrophase; and 3) greater disorderliness of GH release (higher approximate entropy). These distinctive and dynamic reactions to estrogen are consistent with partial withdrawal of IGF-I’s negative feedback and/or accentuated central drive to GH secretion.


Author(s):  
Ferdinand Roelfsema ◽  
Rebecca Yang ◽  
Johannes D Veldhuis

Abstract Context Interleukin-2 (IL2), a proinflammatory cytokine, has been used to treat malignancies. Increased cortisol and ACTH were noted, but GH secretion was not investigated in detail. Objective We quantified GH secretion after a single sc injection of IL2 in 17 young and 18 older healthy men in relation to dose, age and body composition. Design This was a placebo-controlled, blinded, prospectively randomized cross-over study. At 20:00 h IL2 (3 or 6 million units per m2 ) or saline was injected sc. Lights were off between 23:00 and 07:00 h. Blood was sampled at 10-min intervals for 24 h. Outcome measures Deconvolution analysis of GH secretion. Results GH profiles were pulsatile under both experimental conditions and lower in older than young volunteers. Since the effect of IL2 might be time-limited, GH analyses were performed on the complete 24-h series and the 6 h after IL2 administration. Total and pulsatile 24-h GH secretion decreased nonsignificantly. Pulsatile secretion fell over the first 6 h after IL2 (P=0.034), with visceral fat as covariate (P=0.003), but not age(P=0.10). Plots of cumulative 2-h bins of GH pulse mass showed a distinction by treatment and age groups: a temporary GH decrease of 32% and 28% occurred in the first 2-h bins after midnight (P=0.019 and 0.038) in young subjects, while in older subjects no differences were present at any time point. Conclusion This study demonstrates that IL2 temporarily diminishes GH secretion in young, but not elderly, men.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 609-609
Author(s):  
John Apolzan ◽  
Jennifer Rood ◽  
Robbie Beyl ◽  
Shengping Yang ◽  
Frank Greenway ◽  
...  

Abstract Objectives Assess the effects of the amino acid arginine on growth hormone (GH), other metabolites, and mood. Arginine is reported to increase GH, but the mechanism is not known. It was hypothesized prolactin mediated this effect since it is similar in structure to GH and, like GH, is secreted by the pituitary gland. Methods Thirty physically active healthy young males (18–39 y; 18.5–25 kg/m2) were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. Two days prior and 1 day following each treatment a standardized diet was provided that maintained arginine at 3–5 g/d. Arginine or placebo treatments in the form of a beverage were consumed after an overnight fast. Treatment conditions were separated by at least a one week washout period. The beverages contained either 10 g of arginine or 0 g (placebo). Blood was collected at baseline and 1.5, 3.0, and 24 hr post treatment. Plasma GH, prolactin, amino acids, glucose, insulin, triacylglycerols, thyroid hormones, sex hormone binding globulin (SHBG), testosterone, cortisol, and dehydroepiandrosterone (DHEA) were assessed. The Profile of Mood States (POMS) was administered at the same time as blood draws. Repeated measures ANOVAs were used to estimate treatment effects at each time point. Results Arginine increased plasma arginine at 1.5, 3.0, and 24 hr (P ≤ 0.001) and GH at 24 hr (P ˂ 0.05) but not other time points. Arginine increased glucose and insulin at the 1.5 and 3.0 hr (P ˂ 0.05) but not 24 hr. Arginine did not affect any other dependent measure (P &gt; 0.05) including prolactin. When only individuals with detectable levels of GH (responders; n = 16) were analyzed separately, arginine increased GH at the 1.5 (P ˂ 0.05) but not the 3.0 or 24 hr time points. Among the responders, arginine also increased thyroid stimulating hormone (TSH) at the 24 hr time point (P ˂ 0.05) but not the 1.5 and 3.0 hr time points. Conclusions Arginine supplementation modestly increased growth hormone. Despite their similar structures, prolactin secretion was not elevated following arginine supplementation, thus another mechanism is responsible for growth hormone secretion. Funding Sources DoD and NIH P30DK072476. Views expressed are those of the authors and do not reflect official policy of the Army, DoD, or US Government.


2001 ◽  
Vol 280 (1) ◽  
pp. R225-R232 ◽  
Author(s):  
Janneke G. Langendonk ◽  
Johannes D. Veldhuis ◽  
Jacobus Burggraaf ◽  
Rik C. Schoemaker ◽  
Adam F. Cohen ◽  
...  

We compared four common mathematical techniques to determine daily endogenous growth hormone (GH) secretion rates from diurnal plasma GH concentration profiles in 24 women (16 upper- or lower-body obese and 8 normal-weight individuals). Two forms of deconvolution analysis and two techniques based on a priori determined GH clearance estimates were employed. Deconvolution analyses revealed significant differences in the 24-h GH secretion rate between normal-weight and upper-body obese women, whereas the other two techniques did not. Moreover, deconvolution analyses predicted that the reduction in mean plasma GH concentrations in upper-body obese women was accounted for by impaired GH secretion, whereas the other methods suggested that obesity increases GH metabolic clearance. Thus we infer that disparate conclusions concerning GH secretion can be drawn from the same primary data set. The different inferences likely reflect dissimilar kinetic assumptions and the particular limitations intrinsic to each analytical approach. Accordingly, we urge caution in the facile comparison of calculated GH secretion data in humans, especially when kinetic and secretion measurements are performed under different conditions. The most appropriate way to determine the GH secretion rate in humans must be balanced by the exact intent of the experiment and the acceptability of different assumptions in that context.


1984 ◽  
Vol 4 (12) ◽  
pp. 995-1000 ◽  
Author(s):  
Janet E. Merritt ◽  
Pauline R. M. Dobson ◽  
Richard J. H. Wojcikiewicz ◽  
John G. Baird ◽  
Barry L. Brown

A possible role for Ca 2+ and calmodulin in the action of growth-hormone-releasing factor (GHRF) was investigated. Low extracellular Ca2+ (<100 μM), methoxyverapamil, flunarizine, cinnarizine, and Co2+ decreased both basal and GHRF-stimulated growth-hormone secretion, but did not totally inhibit GHRF-stimulation secretion. A calmodulin antagonist, W7, abolished GHRF-stimulated GH secretion, with no effect on basal secretion. It is suggested that GHRF may act primarily by elevating cellular cyclic AMP, which may then modulate calcium mobilization or flux; the increased intracellular Ca2+ concentrations may then activate calmodulin.


1976 ◽  
Vol 50 (4) ◽  
pp. 241-247 ◽  
Author(s):  
J. R. Sutton ◽  
N. L. Jones ◽  
C. J. Toews

1. Seven healthy males were studied during cycle ergometer exercise at 33%, 66% and 90% of V̇o2 max. on three occasions when NH4Cl, NaHCO3 or CaCO3 (as a control substance) were administered in gelatin capsules double blind and in randomized order. Plasma growth hormone (HGH), lactic acid and hydrogen ion concentration ([H+])weremeasured at frequent intervals. 2. Ammonium chloride produced highest blood [H+] and NaHCO3 the lowest. These differences were maintained during exercise and in recovery. Plasma lactic acid concentrations were similar at rest. At 66%, 90% V̇o2 max. and recovery lactic acid was highest with NaHCO3 and lowest with NH4Cl. 3. Exercise stimulated HGH secretion in all studies and the elevation was proportional to the intensity of the exercise. NH4Cl caused a variable elevation of HGH at rest and 33% V̇o2 max. At 66% V̇o2 max., plasma HGH was significantly elevated to similar concentrations in all studies and, at 90% V̇o2 max., HGH was highest with NaHCO3. 4. An infusion of sodium l(+)-lactate producing plasma lactate concentrations of 3–5 mmol/l did not influence HGH secretion. 5. Exercise is a physiological stimulus to HGH secretion and the mechanism is independent of blood [H+] and lactate concentrations.


1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90


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