title: The effect of recombinant human growth hormone and insulin-like growth factor-1 on the mitochondrial function and viability of peripheral blood mononuclear cells in vitro.
abstract: 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 because of an augmentation in the production of mitochondrial-derived free radicals with a subsequent increase in oxidative damage, compromising mitochondrial function. To test this hypothesis, peripheral blood mononuclear cells were incubated for 4 h with either recombinant human GH (rhGH) (range = 0.25-100 μg/L) or recombinant IGF-1 (rIGF-1) (range = 100-600 μg/L) and along with control samples were subsequently analyzed 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 with control samples (lymphocytes: 21.5 ± 1.6 AU; monocytes: 230.2 ± 9.8 AU) following rhGH treatment at both concentrations of 5 μg/L (13.5 ± 1.3 AU, P ≤ 0.05) and 10 μg/L (12.3 ± 1.5 AU, P ≤ 0.05) in lymphocytes and at 10 μg/L (153.4 ± 11.4 AU, 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 2 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.
authors.affiliation: Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Keane
authors.forename: Lotti
authors.initials: L
authors.lastname: Tajouri
authors.forename: Bon
authors.initials: B
authors.lastname: Gray
mesh_terms: D000328:Adult; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D012016:Reference Values; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: apoptose; apoptosis; dopage; doping; membrane potential; physiological; physiologique; pore de transition; potentiel membranaire; superoxide; superoxyde; supra-physiological; supraphysiologique; transition pore