Growth hormone alters components of the glutathione metabolic pathway in dwarf mice
H.M. Brown-Borg and S.G. Rakoczy
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 N. Columbia Rd., Grand Forks, ND 58203, USA
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<0.05), kidney (p<0.01), heart (p<0.005) and liver (p<0.06).
Activity levels of the detoxification enzyme,
glutathione-s-transferase, was also suppressed in kidney tissues at 3
and 12 months of age and in 12 month old dwarf liver tissues (p<0.05).
Taken together, the current results along with data from previous
studies supports a role for growth hormone in the regulation of
antioxidative defense and ultimately, life span in organisms with
altered GH or IGF-1 signaling.
Key words:
dwarf mice, glutathione, growth hormone
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