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Studies were done to assess the contribution of alpha-tocopherol to the regional differences in microsomal lipid peroxidation (LP) and steroid metabolism in the guinea pig adrenal cortex. In normal guinea pigs, ferrous ion (Fe2+)- and ascorbic acid-induced LP are far greater in microsomal preparations from the inner adrenal zone (zona reticularis) than in those from the outer zones (zona fasciculata plus zona glomerulosa). The amounts of unsaturated fatty acids, substrates for LP, are similar in the two zones, but alpha-tocopherol concentrations are 4-5 times greater in outer than inner zone microsomes. Tocopherol depletion by dietary deprivation had little effect on LP in vitro in inner zone microsomes, but substantially increased LP in outer zone preparations. As a result, tocopherol deficiency eliminated the zonal differences in microsomal LP. Unsaturated FFA concentrations were lower in tocopherol-deficient microsomal preparations than in those from tocopherol-sufficient animals, suggesting peroxidative losses in vivo. Tocopherol deficiency decreased steroid C-17,20 lyase activity in outer zone microsomes, but had no effect on activity in inner zone preparations, eliminating the normal zonal difference in activity (outer greater than inner). The results indicate that alpha-tocopherol is a major determinant of adrenal LP and is responsible for the regional differences in microsomal LP in guinea pig adrenal cortex; the effects of ascorbic acid on LP in each zone are also affected by alpha-tocopherol. alpha-Tocopherol may influence the functional zonation of the adrenal cortex by selectively protecting outer zone steroidogenic enzymes from oxidative degradation.

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