Vitamin E, aging and Leydig cell steroidogenesis

Previous studies have suggested that oxidant-induced damage may play a role in the reduced ability of aged Brown Norway rat Leydig cells to produce testosterone. We reasoned that if this was the case, antioxidants such as vitamin E (VE) would be expected to have protective effects on steroidogenesis. To test this hypothesis, the effects of VE on Leydig cell steroidogenesis were examined both in vitro and in vivo. In vitro studies were conducted using Leydig cells isolated from the testes of young adult Brown Norway rats. In one experiment, isolated cells were incubated with luteinizing hormone (LH) alone or with LH plus VE (1.3-40 mu g/ml). At each of 3, 5 and 7 days thereafter, the ability of the cells to produce testosterone was greater in the presence of VE than in its absence, and depended upon VE dose. Culturing the Leydig cells with the antioxidants melatonin or N-tert-butyl-alpha-phenylnitrone also protected Leydig cell steroidogenic function. Additionally, VE was found to suppress Fe2+/sodium ascorbate-induced lipid peroxidation in Leydig cells. These studies strongly supported the contention that VE has a protective effect on Leydig cell steroidogenesis. These in vitro results prompted us to ask whether, in vivo, VE also would affect steroidogenesis as Leydig cells age. To this end, rats were provided one of three diets, begun when the rats were 6 months of age and carried out through age 25 months: VE-deficient, VE-control, or VE-supplemented. The VE-deficient diet had no effect on the age-related reductions in Leydig cell testosterone production observed in VE-control rats. The VE-supplemented diet did not prevent age-related reductions in steroidogenesis, but the reductions at ages 23 and 25 months were significantly less than those seen in Leydig cells from VE-control or VE-deficient rats. Taken together, the results of the in vitro and in vivo studies reported herein are consistent with the conclusion that vitamin E exerts a protective effect on Leydig cell steroidogenesis. (c) 2005 Elsevier Inc. All rights reserved.