Growth hormone alters methionine and glutathione metabolism in Ames dwarf mice

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 methionine and glutathione (GSH) metabolic pathways. Treatment of dwarf mice with GH significantly suppressed methionine adenosyltransferase (40 and 38%) and glycine-N-methyltransferase (44 and 43%) activities (in 3- and 12-month-old mice, respectively). Growth hormone treatment 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 heart and liver. The activity of glutathione-S-transferase, an enzyme involved in detoxification, was also affected by GH treatment. 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.