Pulsatile Intravenous Growth Hormone (GH) Infusion to Hypophysectomized Rats Increases Insulin-Like Growth Factor I Messenger Ribonucleic Acid in Skeletal Tissues More Effectively than Continuous GH Infusion*

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Abstract
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 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 .cntdot. 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 .cntdot. 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.