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从外源性胰岛素样生长因子I(IGF-I)抑制状态下恢复生长激素释放:游离而非结合的IGF-I具有抑制作用的证据。

Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I (IGF-I): evidence for a suppressive action of free rather than bound IGF-I.

作者信息

Chapman I M, Hartman M L, Pieper K S, Skiles E H, Pezzoli S S, Hintz R L, Thorner M O

机构信息

Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

出版信息

J Clin Endocrinol Metab. 1998 Aug;83(8):2836-42. doi: 10.1210/jcem.83.8.5040.

DOI:10.1210/jcem.83.8.5040
PMID:9709956
Abstract

To determine the time course of recovery of GH release from insulin-like growth factor I (IGF-I) suppression, 11 healthy adults (18-29 yr) received, in randomized order, 4-h i.v. infusions of recombinant human IGF-I (rhIGF-I; 3 microg/kg-h) or saline (control) from 25.5-29.5 h of a 47.5-h fast. Serum GH was maximally suppressed within 2 h and remained suppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations were approximately 25% of control day levels [median (interquartile range), 1.2 (0.4-4.0) vs. 4.8 (2.8-7.9) microg/L; P < 0.05]. A rebound increase in GH concentrations occurred 5-7 h after the end of rhIGF-I infusion [7.6 (4.6 -11.7) vs. 4.3 (2.5-6.0) microg/L; P < 0.05]. Thereafter, serum GH concentrations were similar on both days. Total IGF-I concentrations peaked at the end of the rhIGF-I infusion (432 +/- 43 vs. 263 +/- 44 microg/L; P < 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 +/- 36 vs. 202 +/- 23 microg/L; P = 0.001). Free IGF-I concentrations were approximately 140% above control day values at the end of the infusion (2.1 +/- 0.4 vs. 0.88 +/- 0.3 microg/L; P = 0.001), but declined to baseline within 2 h after the infusion. The close temporal association between the resolution of GH suppression and the fall of free IGF-I concentrations, and the lack of any association with total IGF-I concentrations suggest that unbound (free), not protein-bound, IGF-I is the major IGF-I component responsible for this suppression. The rebound increase in GH concentrations after the end of rhIGF-I infusion is consistent with cessation of an inhibitory effect of free IGF-I on GH release.

摘要

为了确定生长激素(GH)释放从胰岛素样生长因子I(IGF-I)抑制中恢复的时间过程,11名健康成年人(18 - 29岁)在47.5小时禁食的25.5 - 29.5小时期间,随机接受4小时的静脉输注,分别输注重组人生长激素(rhIGF-I;3微克/千克·小时)或生理盐水(对照)。在rhIGF-I输注后2小时内,血清GH被最大程度抑制,并在输注后持续抑制2小时;在这4小时期间,GH浓度约为对照日水平的25%[中位数(四分位间距),1.2(0.4 - 4.0)对4.8(2.8 - 7.9)微克/升;P < 0.05]。在rhIGF-I输注结束后5 - 7小时,GH浓度出现反弹升高[7.6(4.6 - 11.7)对4.3(2.5 - 6.0)微克/升;P < 0.05]。此后,两天的血清GH浓度相似。总IGF-I浓度在rhIGF-I输注结束时达到峰值(432 ± 43对263 ± 44微克/升;P < 0.0001),并在rhIGF-I输注后18小时仍保持升高(360 ± 36对202 ± 23微克/升;P = 0.001)。游离IGF-I浓度在输注结束时比对照日值高出约140%(2.1 ± 0.4对0.88 ± 0.3微克/升;P = 0.001),但在输注后2小时内降至基线。GH抑制的解除与游离IGF-I浓度下降之间密切的时间关联,以及与总IGF-I浓度缺乏任何关联,表明未结合(游离)而非蛋白质结合的IGF-I是导致这种抑制的主要IGF-I成分。rhIGF-I输注结束后GH浓度的反弹升高与游离IGF-I对GH释放抑制作用的停止一致。

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