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A Dose-Response Study of Growth Hormone (GH) Replacement on Whole Body Protein and Lipid Kinetics in GH-Deficient Adults

Department of Internal Medicine, Endocrine and Metabolic Sciences, University of Perugia, Perugia; and the National Research Council, Institute for Agroforestry (M.L.), Porano, Italy

Address all correspondence and requests for reprints to: Dr. Pierpaolo De Feo, DIMISEM, Via E. Dal Pozzo, 06126 Perugia, Italy. E-mail: defeo{at}dimisem.med.unipg.it

This study was designed to establish the lower dose of effective GH replacement therapy in severe GH-deficient (GHD) adults. Whole body protein and lipid kinetics were determined in six GHD men in the basal state (B) and after 1 week of treatment with placebo (PL) or 3.3 (GH3.3) or 2 (GH2) µg/kg·day recombinant human GH (rhGH). The rates of whole body proteolysis, oxidation, and synthesis were estimated by infusing [1-¹³C]leucine (prime, 1 mg/kg; infusion rate, 1 mg/kg·h); those of lipolysis (measured in four of the six patients) were estimated by infusing [1,1,2,3,3-D₅]glycerol (prime, 1.8 µmol/kg; infusion rate, 0.06 µmol/kg·min). Serum insulin-like growth factor I (IGF-I) concentrations (picograms per mL; mean ± SE) similarly increased from the basal level (39 ± 7) after 3.3 (108 ± 18) or 2 (109 ± 24) µg/kg·day rhGH (P < 0.001 vs. basal), whereas they did not change with placebo (41 ± 8). Leucine Ra was unaffected by the treatments. GH3.3 reduced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and increased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) and by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no significant effect. In conclusion, 1) at least 3.3 µg/kg·day rhGH are required to increase whole body protein synthesis and lipolysis in male GHD adults; 2) 2 µg/kg·day rhGH normalize serum IGF-I concentrations, but do not modify protein and lipid metabolism; and 3) a normal serum IGF-I concentration does not guarantee that rhGH treatment is also effective on intermediate metabolism.

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