Several antioxidants, both enzymatic and non-enzymatic, are highly expressed in comparison to other tissues. Ascorbic acid (vitamin C), which recycles a-tocopherol (vitamin A) radicals, is present at the highest levels in the adrenal cortex (Hornig 1975), indeed endogenous ascorbic acid was first isolated from adrenal tissue (Svirbely & Szent-Gyorgyi 1932). Depletion of ascorbic acid secondary to vitamin A deficiency in rats leads to adrenocortical degeneration (Gruber et al. 1976).
Maintenance of redox balance is essential for normal cellular functions. Any perturbation in this balance due to increased reactive oxygen species (ROS) leads to oxidative stress and may lead to cell dysfunction/damage/death. Mitochondria are responsible for the majority of cellular ROS production secondary to electron leakage as a consequence of respiration. Furthermore, electron leakage by the cytochrome P450 enzymes may render steroidogenic tissues acutely vulnerable to redox imbalance. The adrenal cortex, in particular, is well supplied with both enzymatic (glutathione peroxidases and peroxiredoxins) and non-enzymatic (vitamins A, C and E) antioxidants to cope with this increased production of ROS due to steroidogenesis. Nonetheless oxidative stress is implicated in several potentially lethal adrenal disorders including X-linked adrenoleukodystrophy, triple A syndrome and most recently familial glucocorticoid deficiency. The finding of mutations in antioxidant defence genes in the latter two conditions highlights how disturbances in redox homeostasis may have an effect on adrenal steroidogenesis. © 2014 The authors.