Growth hormone (GH) has effects on the Central Nervous System (CNS), liver and skin and GH levels decrease with age. Ovariectomy induces further deleterious effects in females. We investigate here the effect of GH, melatonin, estrogens and phytoestrogens on parameters related to oxidative stress and inflammation in the liver, brain and skin in old rats. Old (2 yr) males and females were treated for 10 weeks with GH, melatonin or saline. Ovariectomized females were treated with either GH, melatonin, estrogens, phytoestrogens or saline. Young (2-month) intact females were used as the reference. Gutathione peroxidase, glutathione-S-transferase activities, NO, cytochrome c, caspases 9 and 3, sirtuine, bcl2 and LPO were determined in liver, brain and keratinocytes in culture.

We detected a reduction in the total number of neurones in old rats of both genders (p<0.005) together with a marked reduction of neurogenesis. GH increased the number of neurones without affecting neurogenesis, whereas melatonin enhanced neurogenesis but not the number of neurones. Estrogens and phytoestrogens had the same effect. GH, melatonin and estrogens reduced oxidative stress in cultured hepatocytes of old rats by increasing glutathione peroxidase and transferase and bcl2, and by reducing caspases and NO. Cytosolic cytochrome c was decreased. Cultured keratinocytes from old animals showed enhanced oxidative stress and apoptosis with increased LPO and caspases and reduced bcl2. GH, melatonin and estrogens restored normal values.

In conclusion, GH and melatonin treatment showed beneficial effects on CNS and liver and estrogens and isoflavones prevented oxidative changes in liver tissue, cultured hepatocytes and keratinocytes in ovariectomized females.