Effects of growth hormone on hypothalamic catalase and Cu/Zn superoxide dismutase

Age-associated changes in hypothalamic catalase activity and level, and Cu/ Zn superoxide dismutase (Cu/Zn SOD) activity were examined in Ames dwarf mi ce with growth hormone (GH) deficiency and prolonged lifespan, in PEPCK-hGH transgenic mice with overexpression of GH and reduced lifespan, and compar ed to values measured in normal controls. Hypothalami from young (3-4 month s), middle-aged (9-10 months), and old (19-23 months) male mice were examin ed using spectrophotometric assay and Western blot. In dwarf mice, Cu/Zn SO D and catalase activities declined with age, and were higher than the corre sponding normal values in young and middle-aged groups. Catalase levels als o declined with age, but were similar to values in normal controls. In GH t ransgenic mice, age-associated decline of both catalase and Cu/Zn SOD occur red earlier than in normal animals. Catalase levels and activities in trans genic animals were similar to controls, whereas Cu/Zn SOD activity was high er in transgenics than in normal mice. The present results suggest that dwa rf mice, during early life, have enhanced hypothalamic free radical defense s, which may contribute to their extended lifespan. However, from the prese nt results in GH transgenic mice, it is impossible to conclude whether earl y decline of hypothalamic catalase and Cu/Zn SOD in these animals represent s a correlate of accelerated aging, or contributes to their reduced lifespa n. (C) 2000 Elsevier Science Inc.