Additive Effects of GH and Testosterone on the Anabolic Changes of Puberty: A Metabolic Study † 459

Abstract

During human puberty there is a dramatic rise in GH sex steroids concentrations and in GH production rates and IGF-1. These studies were designed to investigate the relative contributions of testosterone (T) and GH on the metabolic changes of puberty. 6 boys with GH deficiency (defined as profound growth retardation (>-2.5 Height SDS), poor growth velocity and peak GH responses to secretagogues <7ng/ml) were studied (mean age: 12±0.7 yrs). Mean bone age at entry was: 10.4±0.8 yrs. After a weight maintenance diet for 3d prior to admission, patients were admitted to the Research Unit. The next a.m., after an overnight fast, whole body protein kinetics were studied using a stable isotope of leucine (13C-leu) for 4 hrs and frequent blood, breath and urine samples obtained as well as indirect calorimetry. Body composition was measured by Bioelectrical Impedance Analysis(BIA), calipers and DEXA scan. After the baseline study (D1), the boys were begun on T enanthate, 50-75mg IM, dose repeated in 3w, and the study repeated identically within 4w of D1 (D2). After D2, the boys were begun on daily SQ injections of rhGH (Nutropin, Genentech) at 0.3mg/kg.w while T Rx was continued. After another 4w, studies were repeated a 3rd time(D3), each subject as their own control. Four patients have completed these studies thus far. Fat free mass (FFM) by BIA increased after T Rx (+5%), and +12% after T/GH Rx (p=0.002 vs D1), with a concomitant decrease in%FM after T Rx (-11%), with an even greater decline as compared to baseline on D3 (-25%, p=0.03). Rates of whole body proteolysis (Leucine Ra) did not change after T Rx (+2%) and increased +18% after T/GH Rx (p=0.08); leucine oxidation decreased on D2 (-28%, p=0.06), and declined even further after D3(-36%, p=0.02); and non-oxidative leucine disposal, a measure of protein synthesis, increased modestly on D2 (+10%), and +32% on D3 (p=0.03). These changes paralleled the decrease in protein oxidation rates on D2 (-31%, p=0.05), and even greater decline on D3 (-41%, p=0.014). Plasma IGF-1 concentrations increased significantly after T Rx (+70%) and even more after T/GH Rx (+182%, p=0.03). In summary: T and GH appear to have additive effects on body composition, protein anabolism and IGF-1 generation. In conclusion: Preliminary studies suggest that GH and T can independently affect body composition in males.