Synergistic effects of testosterone and growth hormone on protein metabolism and body composition in prepubertal boys

During human puberty there is a substantial increase in growth hormone (GH) and sex steroidal hormone concentrations, as well as in GH production rates and insulin-like growth factor-I (IGF-I). These studies were designed to investigate some of the interactions of testosterone (T) and GH in the metabolic changes of puberty. Ten boys with severe GH deficiency (GHD) were studied (mean age, 12.5 ± 0.5 years) using stable isotope infusions, indirect calorimetry, and body composition analysis. After the baseline study, they received 2 doses of T enanthate (50 to 75 mg, intramuscular [IM]), and they were studied again 4 weeks later. The boys were then begun on daily subcutaneous (SC) GH (0.3 mg/kg/wk), while T therapy was continued for another 4 weeks and the studies repeated a third time. The treatment order was randomized. Protein oxidation rates decreased after T alone (-28%, P < .01), decreasing further after combined T/GH treatment (-36% v baseline, P < .01). The nonoxidative leucine disposal (NOLD), a measure of whole body protein synthesis, increased significantly after combined T/GH regardless of treatment order. The combination of T/GH also resulted in greater changes in body composition than T alone, with comparable decreases in %FM and corresponding increases in fat free mass (FFM). Measures of carbohydrate (CHO) metabolism, including glucose production and oxidation rates, were unaffected by either T or T/GH combination. Plasma IGF-I concentrations increased after T treatment and even more after T/GH combination, regardless of the treatment order. In conclusion GH and T are synergistic on whole body protein anabolism and body composition in males, even at a young age, but the positive effects of T on protein anabolism and body composition appear to need a basal amount of GH for those effects to be observed. GH and T both potentiate the development of the full body composition and metabolic changes of puberty.