Isgaard J, Carlsson L, Isaksson O G, Jansson J O
Department of Physiology, University of Göteborg, Sweden.
Endocrinology. 1988 Dec;123(6):2605-10. doi: 10.1210/endo-123-6-2605.
In this study we have investigated a possible functional role of the plasma pattern of GH in regulation of insulin-like growth factor I (IGF-I) mRNA in liver, skeletal muscle, and rib growth plate of the rat. Hypophysectomized male rats given T4 and glucocorticoid replacement therapy were equipped with indwelling jugular venous cannulae attached via swivels to a multichannel pumping system programmed to deliver human GH in a continuous or pulsatile (one pulse per 3 h) pattern for 5 days. At the end of the experiment, skeletal muscle, rib growth plates, and liver from intact and hypophysectomized rats were homogenized, and total nucleic acid was prepared. IGF-I mRNA was quantitated by solution hybridization assay using a RNA probe radiolabeled with [35S]UTP. Pulsatile treatment with GH in a dose of 1.5 U/kg.day induced a 3- to 5-fold increase in the levels of IGF-I mRNA in skeletal muscle and rib growth plates. In contrast, continuous infusion with GH was much less effective in these tissues. In the liver both continuous and pulsatile GH infusion significantly elevated the amount of IGF-I mRNA, and there was no significant difference between these two treatments. In the tissues studied similar results were obtained with a higher dose of GH (3.0 U/kg.day). Pulsatile GH treatment stimulated longitudinal bone growth more effectively than continuous GH treatment, confirming earlier studies. It is concluded that pulsatile GH treatment is more effective than continuous GH infusion in increasing IGF-I mRNA levels in rib growth plate and skeletal muscle, i.e. two major target organs for the anabolic effects of GH.
在本研究中,我们调查了大鼠肝脏、骨骼肌和肋骨生长板中生长激素(GH)的血浆模式在调节胰岛素样生长因子I(IGF-I)mRNA方面可能的功能作用。接受甲状腺素(T4)和糖皮质激素替代治疗的垂体切除雄性大鼠,通过旋转接头连接到多通道泵系统,该系统被编程为以连续或脉冲式(每3小时一个脉冲)模式输送人生长激素,持续5天。实验结束时,将完整和垂体切除大鼠的骨骼肌、肋骨生长板和肝脏匀浆,并制备总核酸。使用用[35S]UTP放射性标记的RNA探针通过溶液杂交测定法定量IGF-I mRNA。以1.5 U/kg·天的剂量脉冲式给予生长激素可使骨骼肌和肋骨生长板中IGF-I mRNA水平增加3至5倍。相比之下,在这些组织中持续输注生长激素的效果要差得多。在肝脏中,持续和脉冲式输注生长激素均显著提高了IGF-I mRNA的量,且这两种治疗之间无显著差异。在研究的组织中,使用更高剂量的生长激素(3.0 U/kg·天)也获得了类似的结果。脉冲式生长激素治疗比持续生长激素治疗更有效地刺激纵向骨生长,这证实了早期的研究。得出的结论是,在增加肋骨生长板和骨骼肌(即生长激素合成代谢作用的两个主要靶器官)中IGF-I mRNA水平方面,脉冲式生长激素治疗比持续输注生长激素更有效。