The role of growth hormone in the regulation of the anaerobic energy system and physical function

Abstract

Growth hormone (GH) regulates energy metabolism and body composition in adult life. Adults with GH deficiency (GHD) suffer from lack of energy and from impaired physical functioning. GH supplementation improves sprinting in recreational athletes, a performance measure dependent on the anaerobic energy system (AES). The AES underpins the initiation of all physical activities including those of daily living. The physiological and functional significance of GH in regulation of the AES is unknown. This thesis tests the hypothesis that GH positively regulates the AES and aspects of physical functioning in adult life. The key objectives are to 1) investigate whether anaerobic capacity is impaired in adults with GHD and improved by GH replacement, ii) characterise facets of physical function that are AES-dependent and GH responsive and iii) identify GH-regulated genes governing anaerobic metabolism in skeletal muscle. Exercise capacity, body composition, physical function and quality of life (QoL) were studied in 19 adults with GHD before and after GH replacement. Anaerobic capacity was assessed by the 30-second Wingate test, and aerobic capacity by the VO2max test. Physical function was assessed by the stair-climb test, chair-stand test, and 7-day pedometry. QoL was assessed by a GHD-specific questionnaire. Lean body mass (LBM) was quantified by dual-energy x-ray absorptiometry. Muscle biopsies were obtained before and after 1 and 6 months of GH replacement. GH responsive genes were identified by microarray analysis. In a cross-sectional study, anaerobic capacity and aerobic capacity were significantly reduced compared to age-, gender- and body mass index-matched normal adults. The duration of the stair climb test was longer, the number of chair stand repetitions and daily step counts were lower in adults with GHD who had lower QoL scores. GH status was an independent predictor of anaerobic capacity, which significantly and independently correlated with stair climb performance and QoL. One month of GH replacement (0.5 mg/day) did not significantly change anaerobic capacity nor any of the other outcome measures compared to placebo in adults with GHD. Six months of GH treatment significantly increased LBM, anaerobic capacity, chair-stand repetitions, daily step count, and QoL scores but not VO2max. Improvement in anaerobic capacity significantly correlated with an improvement in the energy and vitality domains of QoL. GH treatment did not significantly affect the differential expression of metabolic genes in skeletal muscle. In summary, anaerobic capacity, aerobic capacity, physical function and QoL were impaired in adults with GHD. GH replacement improved anaerobic capacity, LBM, chair-stand performance, daily step counts and QoL in a time-dependent manner without a concomitant improvement in aerobic capacity. GH at a replacement dose was insufficient to induce the detection of GH-regulated genes governing substrate metabolism and energy production in skeletal muscle. In conclusion, GH positively regulates the AES, which improves selective aspects of physical function influencing QoL in adult humans.