Growth Hormone Alters Components of the Glutathione Metabolic Pathway in Ames Dwarf Micea

Authors

  • HOLLY M. BROWN-BORG,

    Corresponding author
    1. Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203, USA
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  • SHARLENE G. RAKOCZY,

    1. Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58203, USA
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  • ERIC O. UTHUS

    1. U.S. Department of Agriculture, ARS, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58203, USA
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  • a

    The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area is an equal opportunity/affirmative action employer and all agency services are available without discrimination.

  • Mention of a trademark or proprietary product does not constitute a guarantee of warranty of the product by the United States Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.

Address for correspondence: Holly M. Brown-Borg, Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 N. Columbia Road, Grand Forks, ND 58203. Voice: 701-777-3949; fax: 701-777-4490. brownbrg@medicine.nodak.edu

Abstract

Abstract: Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1(IGF-1)/insulin pathway is associated with extended life span in several species. Ames dwarf mice are GH and IGF-1 deficient and live 50-64% longer than wild-type littermates (males and females, respectively). Previously, we have shown that Ames mice exhibit elevated levels of antioxidative enzymes and lower oxidative damage. To further explore the relationship between GH and antioxidant expression, we administered GH or saline to dwarf mice and evaluated components of the glutathione (GSH) synthesis and degradation system. Growth hormone treatment significantly elevated kidney gamma-glutamyl-cysteine synthetase protein levels in 3- and 12-month-old dwarf mice. In contrast, the activity of the GSH degradation enzyme, gamma-glutamyl transpeptidase, was suppressed by GH administration in brain (P < .05), kidney (P < .01), heart (P < .005), and liver (P < .06). Activity levels of the detoxification enzyme, glutathione-S-transferase, were also suppressed in kidney tissues at 3 and 12 months of age and in 12-month-old dwarf liver tissues (P < .05). Taken together, the current results along with data from previous studies support a role for growth hormone in the regulation of antioxidative defense and, ultimately, life span in organisms with altered GH or IGF-1 signaling.

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