Jørgensen J O, Blum W F, Møller N, Ranke M B, Christiansen J S
Second University Clinic of Internal Medicine, Aarhus Kommunehospital, Denmark.
J Clin Endocrinol Metab. 1991 Mar;72(3):582-7. doi: 10.1210/jcem-72-3-582.
Virtually all circulating insulin-like growth factors I and II (IGF-I and IGF-II) are bound to specific binding proteins (IGFBP), of which IGFBP-3 is the quantitatively most important. The mechanisms regulating the close coordination between serum levels of IGFs and IGFBP-3 is poorly understood. We therefore evaluated the temporal association of serum IGF-I, IGF-II, and IGFBP-3 measured by RIAs after well defined short-term GH exposure in GH-deficient patients. Six patients (mean +/- SE age: 20.5 +/- 1.1 yr) each underwent three GH study protocols in random order. Each study was preceded by 4 weeks without GH therapy. Two units of GH were administered iv as either: 1) two boluses, 2) eight boluses, or 3) a constant infusion. The duration of each study was 44 h including at least 16 h after termination of GH administration. Increments in serum IGF-I occurred 4-6 h after initiated GH exposure in all studies. In the two-bolus study the IGF-I increase was modest with mean +/- SE peak values of 12.4 +/- 2.1 nmol x L-1 after GH administration. In the eight bolus and constant infusion studies significantly higher IGF-I levels were generated: 17.0 +/- 2.2 nmol x L-1 (8 bolus) and 18.8 +/- 1.1 h nmol x L-1 (infusion). In contrast the time course change in serum IGF-II did not differ in the three studies, and it was characterised by a sluggish increase of approximately 30% evidenced after 16-20 h. The changes in IGFBP-3 were almost identical in the three studies. After a lag phase of approximately 18-20 h a gradual increase of approximately 40%, which had not ceased at the end of the study period, was observed. The molar ratio of serum IGF-I plus IGF-II:serum IGFBP-3 remained constant with values between 0.8-0.9 except in the constant infusion experiment, in which the ratio increased significantly with time reaching a mean peak value, which exceeded 1.0, after 24 h. Our data suggest that a pulsatile GH pattern is not superior to constant GH levels as regards generation of IGFs and IGFBP. The earlier increase in serum IGF-I compared to IGF-II and IGFBP-3 suggests that IGF-I may be the main regulator of IGFBP-3 production. Accordingly, the slow increase in serum IGF-II, which paralleled that of IGFBP-3, could indicate that serum IGF-II levels mainly depend on the concentration or binding site availability of IGFBP-3.
实际上，所有循环中的胰岛素样生长因子I和II（IGF-I和IGF-II）都与特定的结合蛋白（IGFBP）结合，其中IGFBP-3在数量上最为重要。调节IGF和IGFBP-3血清水平之间密切协调的机制尚不清楚。因此，我们评估了在明确的短期生长激素（GH）暴露后，通过放射免疫分析法（RIA）测定的GH缺乏患者血清IGF-I、IGF-II和IGFBP-3的时间关联。6名患者（平均±标准误年龄：20.5±1.1岁），每人随机接受三种GH研究方案。每项研究前4周不进行GH治疗。静脉注射2单位GH，方式如下：1）两次推注；2）八次推注；3）持续输注。每项研究持续44小时，包括GH给药结束后至少16小时。在所有研究中，GH暴露开始后4 - 6小时血清IGF-I升高。在两次推注研究中，IGF-I升高幅度较小，GH给药后平均±标准误峰值为12.4±2.1 nmol/L。在八次推注和持续输注研究中，产生的IGF-I水平显著更高：17.0±2.2 nmol/L（八次推注）和18.8±1.1 nmol/L（输注）。相比之下，三项研究中血清IGF-II的时间进程变化无差异，其特点是在16 - 20小时后缓慢升高约30%。三项研究中IGFBP-3的变化几乎相同。在大约18 - 20小时的延迟期后，观察到逐渐升高约40%，在研究期结束时仍未停止。血清IGF-I加IGF-II与血清IGFBP-3的摩尔比保持恒定，值在0.8 - 0.9之间，但在持续输注实验中除外，在该实验中该比值随时间显著增加，24小时后达到平均峰值，超过1.0。我们的数据表明，就IGF和IGFBP的产生而言，脉冲式GH模式并不优于恒定的GH水平。血清IGF-I比IGF-II和IGFBP-3更早升高，这表明IGF-I可能是IGFBP-3产生的主要调节因子。因此，血清IGF-II的缓慢升高与IGFBP-3平行，这可能表明血清IGF-II水平主要取决于IGFBP-3的浓度或结合位点可用性。
