Stimulation of the 150-kilodalton insulin-like growth factor-binding protein-3 ternary complex by continuous and pulsatile patterns of growth hormone (GH) administration in GH-deficient patients.
Stimulation of the 150-kilodalton insulin-like growth factor-binding protein-3 ternary complex by continuous and pulsatile patterns of growth hormone (GH) administration in GH-deficient patients.
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DOI：
10.1210/jcem.85.11.6957
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发表时间：
2000-11
期刊：
影响因子：
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通讯作者：
T. Laursen;A. Flyvbjerg;J. Jørgensen;R. Baxter;J. Christiansen
中科院分区：
文献类型：
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作者：
T. Laursen;A. Flyvbjerg;J. Jørgensen;R. Baxter;J. Christiansen
在循环中，胰岛素样生长因子I（IGF-I）、胰岛素样生长因子结合蛋白3（IGFBP-3）和酸不稳定亚基（ALS）形成150-kDa三元复合物，该三元复合物对于调节IGF-I生物活性是重要的。已知GH给药可增加三元复合物的单个组分，并且在GH缺乏大鼠中，150-kDa复合物的形成更多地由连续GH模式诱导，而不是由脉冲GH模式诱导。本研究的目的是研究GH给药模式对人体150 kDa三元复合物形成的影响。5例GH缺乏患者在24 h内随机静脉给予固定总GH剂量（2 IU/m2-24 h），1）连续输注或2）8次推注。GH给药显著增加血清IGF-I和IGFBP-3水平以及IGF-I/IGFBP-3比值。连续用药后IGF-I水平升高最显著（P < 0.01）。血清ALS水平从94+/-21增加到180+/-29（输注）和从85+/-17增加到155+/-17 nmol/L（脉冲）显著增加（均P < 0.005）。采用中性尺寸排阻色谱法能够分离三元复合物和非复合物结合级分中的IGFBP-3。GH给药后三元复合物中的IGFBP-3显著增加[输注期间增加44%（P = 0.048），推注期间增加62%（P = 0.004）]。然而，GH给药后，非复合物相关IGFBP-3组分并未显著增加（P = NS）。最后，三元复合物的形成不受GH递送模式的影响。总之，短期GH给药增加了150 kDa三元复合物的所有成分。恒定GH暴露后较高水平的IGF-I可能表明结合分数增加。然而，GH模式并不影响三元复合物本身的诱导。根据三元复合物组分的水平判断，在长期GH治疗期间，连续和间歇GH模式在临床上可能同样有效。
In the circulation insulin-like growth factor I (IGF-I), IGF-binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS) form a 150-kDa ternary complex that is of importance for the regulation of IGF-I bioactivity. GH administration is known to increase each of the single components of the ternary complex, and in GH-deficient rats formation of the 150-kDa complex is induced more by continuous than by pulsatile GH patterns. The aim of the present studies was to study the effects of the GH administration pattern on the formation of the 150-kDa ternary complex in humans. A fixed total GH dose (2 IU/m2-24 h) was administered iv randomly as 1) continuous infusion or 2) eight bolus injections to five GH-deficient patients over a period of 24 h. GH administration significantly increased serum IGF-I and IGFBP-3 levels and the IGF-I/IGFBP-3 ratio. IGF-I levels increased most pronouncedly after continuous administration (P < 0.01). Serum ALS levels increased significantly (both P < 0.005) from 94+/-21 to 180+/-29 (infusion) and from 85+/-17 to 155+/-17 nmol/L (pulses). Employment of neutral size exclusion chromatography enabled separation of IGFBP-3 in ternary complex and noncomplex-bound fractions. IGFBP-3 in the ternary complex increased significantly after GH administration [by 44% (P = 0.048) during infusion and by 62% (P = 0.004) during bolus]. The noncomplex-associated IGFBP-3 fraction, however, did not increase significantly after GH administration (P = NS). Finally, formation of the ternary complex was unaffected by the pattern of GH delivery. In conclusion, short-term GH administration increased all components of the 150-kDa ternary complex. Higher levels of IGF-I after constant GH exposure could indicate an increased bound fraction. However, the GH pattern did not influence the induction of the ternary complex itself. Continuous and intermittent GH patterns may be clinically equally effective during long-term GH therapy, as judged by levels of the components of the ternary complex.