Abstract
The aim of this study is to evaluate the effect of growth hormone therapy (rGH) on mitochondrial function on peripheral muscle and to correlate with exercise capacity in subjects with severe adult growth hormone deficiency (GHD). Six months, double-blind, randomized, crossover, placebo-controlled trial of subcutaneous rGH in 17 patients with GHD. Quadriceps muscle biopsies were obtained at baseline, 3 months, and 6 months to measure succinate dehydrogenase (SDH) to assess mitochondrial activity. Exercise capacity was measured with cardiopulmonary exercise testing. Lipids, glycemic parameters, and body fat levels were also measured. Serum insulin-like growth factor 1 (IGF1) levels reduced fat mass by 3.2% (p < 0.05) and normalized with rGH in the active phase (p < 0.005). Patients showed an increase in SDH (p < 0.01) from base line that differed between placebo and rGH therapy treatment groups (p < 0.05): those treated by rGH followed by placebo showed a significant increase in SDH (p < 0.001) followed by a decrease, with a significant between group difference at the end of 6 months (p < 0.05). No significant improvements or correlation with exercise capacity was found. Short-term rGH for 3 months normalized IGF1 levels, reduced fat mass, and had a significant effect on mitochondrial function, but exercise capacity was unchanged. Number ISRCTN94165486.
Highlights
Patients with hypopituitarism have reduced life expectancy when compared to the general population, mainly attributed to cerebrovascular and cardiovascular disease [1, 2]
The aim of this study is to evaluate the effect of growth hormone therapy on mitochondrial function on peripheral muscle and to correlate with exercise capacity in subjects with severe adult growth hormone deficiency (GHD)
Patients with GHD are exposed to an abnormal metabolic environment that is likely to perpetuate high levels of reactive oxygen species (ROS), downregulating insulin-like growth factor 1 (IGF1)-1 signaling further and increasing oxidative stress and mitochondrial dysfunction
Summary
Patients with hypopituitarism have reduced life expectancy when compared to the general population, mainly attributed to cerebrovascular and cardiovascular disease [1, 2] The cause of this is unclear but induced mitochondrial dysfunction due to increased oxidized LDL, hypertriglyceridemia, and hyperglycemia seen in growth hormone deficiency (GHD) may trigger an increase in mitochondrial reactive oxygen species (ROS) and superoxide molecules formation. SDH deficiency is associated with mitochondrial disorders that mainly affect organ dependant on oxidative metabolism such as brain, skeletal muscle, and cardiac muscle [4], and it is sensitive to inhibition by ROS complexes [5]. This mitochondrial dysfunction may decrease aerobic capacity and endothelial dysfunction/apoptosis [5]
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