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

James Keane, Lotti Tajouri, Bon Gray

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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.

Original languageEnglish
Pages (from-to)105-115
Number of pages11
JournalApplied Physiology, Nutrition and Metabolism
Volume40
Issue number2
DOIs
Publication statusPublished - 16 Oct 2014

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Human Growth Hormone
Somatomedins
Growth Hormone
Blood Cells
Free Radicals
Monocytes
Lymphocytes
Mitochondrial Membrane Potential
Insulin-Like Growth Factor I
Superoxides
Flow Cytometry
Mitochondria
Antioxidants
Hormones
In Vitro Techniques
mitochondrial permeability transition pore

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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.",
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N2 - 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.

AB - 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.

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