scholarly journals Overtrained horses alter their resting pulsatile growth hormone secretion

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.

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.


2008 ◽  
Vol 93 (11) ◽  
pp. 4471-4478 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Daniel M. Keenan ◽  
Joy N. Bailey ◽  
Adenborduin Adeniji ◽  
John M. Miles ◽  
...  

Background: Why pulsatile GH secretion declines in estrogen-deficient postmenopausal individuals remains unknown. One possibility is that estrogen not only enhances stimulation by secretagogues but also attenuates negative feedback by systemic IGF-I. Site: The study took place at an academic medical center. Subjects: Subjects were healthy postmenopausal women (n = 25). Methods: The study included randomized assignment to estradiol (n = 13) or placebo (n = 12) administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and 2.0 mg/m2 recombinant human IGF-I sc on separate days fasting. Analysis: Deconvolution analysis of pulsatile and basal GH secretion and approximate entropy (pattern-regularity) analysis were done to quantify feedback effects of IGF-I. Outcomes: Recombinant human IGF-I injections increased mean and peak serum IGF-I concentrations dose dependently (P &lt; 0.001) and suppressed mean GH concentrations (P &lt; 0.001), pulsatile GH secretion (P = 0.001), and approximate entropy (P &lt; 0.001). Decreased GH secretion was due to reduced secretory-burst mass (P = 0.005) and frequency (P &lt; 0.001) but not basal GH release (P = 0.52). Estradiol supplementation lowered endogenous, but did not alter infused, IGF-I concentrations while elevating mean GH concentrations (P = 0.012) and stimulating pulsatile (P = 0.008) and basal (P &lt; 0.001) GH secretion. Estrogen attenuated IGF-I’s inhibition of pulsatile GH secretion (P = 0.042) but was unable to restore physiological GH pulse frequency or normalize approximate entropy. Conclusion: Short-term estrogen replacement in postmenopausal women selectively mutes IGF-I-mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.


2002 ◽  
Vol 282 (4) ◽  
pp. E943-E951 ◽  
Author(s):  
Hiralal G. Maheshwari ◽  
Suzan S. Pezzoli ◽  
Asad Rahim ◽  
Stephen M. Shalet ◽  
Michael O. Thorner ◽  
...  

Growth hormone (GH) secretion is regulated by GH-releasing hormone (GHRH), somatostatin, and possibly ghrelin, but uncertainty remains about the relative contributions of these hypophysiotropic factors to GH pulsatility. Patients with genetic GHRH receptor (GHRH-R) deficiency present an opportunity to examine GH secretory dynamics in the selective absence of GHRH input. We studied circadian GH profiles in four young men homozygous for a null mutation in the GHRH-R gene by use of an ultrasensitive GH assay. Residual GH secretion was pulsatile, with normal pulse frequency, but severely reduced amplitude (<1% normal) and greater than normal process disorder (as assessed by approximate entropy). Nocturnal GH secretion, both basal and pulsatile, was enhanced compared with daytime. We conclude that rhythmic GH secretion persists in an amplitude-miniaturized version in the absence of a GHRH-R signal. The nocturnal enhancement of GH secretion is likely mediated by decreased somatostatin tone. Pulsatility of residual GH secretion may be caused by oscillations in somatostatin and/or ghrelin; it may also reflect intrinsic oscillations in somatotropes.


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.


2011 ◽  
Vol 300 (6) ◽  
pp. E1069-E1075 ◽  
Author(s):  
Claire E. H. M. Donjacour ◽  
N. Ahmad Aziz ◽  
Ferdinand Roelfsema ◽  
Marijke Frölich ◽  
Sebastiaan Overeem ◽  
...  

Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems and body composition. Additionally, growth hormone (GH) alterations my influence weight in narcolepsy. Symptoms can be treated effectively with sodium oxybate (SXB; γ-hydroxybutyrate) in many patients. This study compared growth hormone secretion in patients and matched controls and established the effect of SXB administration on GH and sleep in both groups. Eight male hypocretin-deficient patients with narcolepsy and cataplexy and eight controls matched for sex, age, BMI, waist-to-hip ratio, and fat percentage were enrolled. Blood was sampled before and on the 5th day of SXB administration. SXB was taken two times 3 g/night for 5 consecutive nights. Both groups underwent 24-h blood sampling at 10-min intervals for measurement of GH concentrations. The GH concentration time series were analyzed with AutoDecon and approximate entropy (ApEn). Basal and pulsatile GH secretion, pulse regularity, and frequency, as well as ApEn values, were similar in patients and controls. Administration of SXB caused a significant increase in total 24-h GH secretion rate in narcolepsy patients, but not in controls. After SXB, slow-wave sleep (SWS) and, importantly, the cross-correlation between GH levels and SWS more than doubled in both groups. In conclusion, SXB leads to a consistent increase in nocturnal GH secretion and strengthens the temporal relation between GH secretion and SWS. These data suggest that SXB may alter somatotropic tone in addition to its consolidating effect on nighttime sleep in narcolepsy. This could explain the suggested nonsleep effects of SXB, including body weight reduction.


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.


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.


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


1980 ◽  
Vol 93 (2) ◽  
pp. 134-138 ◽  
Author(s):  
M. Donnadieu ◽  
R. M. Schimpff ◽  
P. Garnier ◽  
J. L. Chaussain ◽  
J. C. Job

Abstract. Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = −0.711, P < 0.001) and was preceded by a fall of Tf (r = −0.610, P < 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginineinduced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = −0.608, P < 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P < 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.


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