Abstract
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.
Highlights
Reactive oxygen species (ROS) are derived from O2 and comprise molecules with varying oxidant properties
Disturbances in redox homeostasis within the adrenocortical environment may have an effect on steroidogenesis, as evidenced by several disorders of adrenal insufficiency, including most recently familial glucocorticoid deficiency (FGD)
It has been proposed that this mechanism of redox signalling exerts physiological control over steroidogenesis at the level of the adrenal gland, in addition to the well-characterised negative feedback exerted by cortisol on the hypothalamic– pituitary–adrenal (HPA) axis
Summary
Reactive oxygen species (ROS) are derived from O2 and comprise molecules with varying oxidant properties. Oxidative stress occurs when this balance is disturbed. Oxidative stress is implicated in a plethora of conditions including neurodegenerative disorders, diabetes mellitus, cardiovascular disease and ageing. In comparison to many other tissues, including those with high metabolic demand such as the liver and brain, the adrenal cortex has high levels of several antioxidants, both enzymatic and non-enzymatic. This investment is necessary given the high turnover of lipid within the mitochondria and ROS production during steroidogenesis. Disturbances in redox homeostasis within the adrenocortical environment may have an effect on steroidogenesis, as evidenced by several disorders of adrenal insufficiency, including most recently familial glucocorticoid deficiency (FGD)
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