This study investigated whether the putative physiological benefits induced by growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are countered at supra-physiological concentrations due to an augmentation in the production of mitochondrial-derived free radicals with a subsequent increase in oxidative damage compromising mitochondrial function. In order to test this hypothesis, peripheral blood mononuclear cells (PBMCs) were incubated for 4 hours with either recombinant human growth hormone (rhGH) (Range = 0.25 – 100µg/L) or recombinant IGF-1 (rIGF-1) (Range = 100 – 600µg/L) and along with control samples were subsequently analysed by flow cytometry for the determination of cellular viability, mitochondrial membrane potential (Δψm), mitochondrial superoxide (O2−) generation and mitochondrial permeability transition pore (mtPTP) activity. Results showed levels of mitochondrial O2− generation to be significantly reduced compared to control samples (lymphocytes – 21.5±1.6AU / monocytes – 230.2±9.8AU) following rhGH treatment at both concentrations of 5µg/L (13.5±1.3AU, P≤0.05) and 10µg/L (12.3±1.5AU, P≤0.05) in lymphocytes and at 10µg/L (153.4±11.4AU, P≤0.05) in monocytes. However, no significant effect was found at either higher rhGH concentrations or following treatment with any concentration of rIGF-1. In addition, neither of the two hormones had any significant effect on Δψm, mtPTP activity or on cellular viability. In conclusion, physiological concentrations of rhGH elicited a protective cellular effect through the reduction of oxidative free radicals within mitochondria. This antioxidant effect was diminished at supra-physiological concentrations but not to a level that would elicit disruption of mitochondrial function.
Available at: http://works.bepress.com/lotti_tajouri/28/