Evidence for acyl-ghrelin modulation of growth hormone release in the fed state

Evidence for acyl-ghrelin modulation of growth hormone release in the fed state
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DOI:
10.1210/jc.2007-2234
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发表时间:
2008-05-01
影响因子:
5.8
通讯作者:
Thorner, Michael O.
Thorner, Michael O.
中科院分区:
医学2区
文献类型:
--
作者:
Nass, Ralf;Farhy, Leon S.;Thorner, Michael O.

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研究背景:生长激素释放激素(GHRH)和生长抑素调节生长激素分泌的时间和频率。这项研究提供了证据,这些生长激素脉冲放大内源性酰基-ghrelin.Design:血液采样每10分钟为26.5小时,在一个标准化的膳食,并在最后24小时的61.5小时的快速进料。GH分泌曲线来自10分钟采样数据的去卷积,全长酰基-ghrelin水平使用新开发的双位点夹心测定法进行测量。设置:该研究在大学医院综合临床研究中心进行。参与者:参与者包括8名男性,平均(+/- SD)年龄为24.5 ± 3.7岁(体重指数24 +/- 2.1 kg/m(2))。计算了各个GH分泌事件的幅度和每个GH爆发前60分钟间隔内的平均酰基-ghrelin浓度之间的相关性。在进食状态下,所有受试者的峰值相关性均为正,并且当酰基-ghrelin水平下降时,峰值相关性显著高于空腹状态[平均值(+/- SEM):0.7(0.04)vs. 0.29(0.08),P = 0.017]。此外,长期禁食与生长激素分泌脉冲质量和幅度增加有关,但与频率无关[进食与禁食脉冲质量:0.22(0.05)vs. 0.44(0.06)μ g/L,P = 0.002;振幅:5.2(1.3)与11.8(1.9)μ g/L/min,P = 0.034;每24小时脉冲数:19.4(0.5)vs. 22.0(1.4),P = 0.1]。结论:我们的数据支持这一假设,即在正常条件下,在正常饮食的受试者中,生长素释放肽的作用是增加GH脉冲的幅度。
Context: The timing and frequency of GH secretory episodes is regulated by GHRH and somatostatin. This study provides evidence for amplification of these GH pulses by endogenous acyl-ghrelin.Design: Blood was sampled every 10 min for 26.5 h during a fed admission with standardized meals and also during the final 24 h of a 61.5-h fast. GH secretion profiles were derived from deconvolution of 10-min sampling data, and full-length acyl-ghrelin levels were measured using a newly developed two-site sandwich assay.Setting: The study was conducted at a university hospital general clinical research center.Participants: Participants included eight men with mean (+/- SD) age 24.5 +/- 3.7 yr (body mass index 24 +/- 2.1 kg/m(2)).Results: Correlations were computed between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-min interval preceding each GH burst. In the fed state, the peak correlations were positive for all subjects and significantly higher than in the fasting state when acyl-ghrelin levels declined [mean (+/- SEM): 0.7 (0.04) vs. 0.29 (0.08), P = 0.017]. In addition, long-term fasting was associated with an increase in the GH secretory pulse mass and amplitude but not frequency [fed vs. fasting pulse mass: 0.22 (0.05) vs. 0.44 (0.06) mu g/liter, P = 0.002; amplitude: 5.2(1.3) vs. 11.8 (1.9) mu g/liter/min, P = 0.034; pulses per 24 h: 19.4 (0.5) vs. 22.0 (1.4), P = 0.1].Conclusion: Our data support the hypothesis that under normal conditions in subjects given regular meals endogenous acyl-ghrelin acts to increase the amplitude of GH pulses.