Oxidative stress and adrenocortical insufficiency

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.

Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress

“…In recent years, accumulating evidence indicates that oxidative stress resulting from an imbalance between pro-oxidants and anti-oxidants plays an important role in the pathogenesis of adrenal insufficiency [6,7]. As a result, overproduction of reactive oxygen species (ROS) can oxidize thiols, lipids, proteins and nucleic acids, consequently leading to oxidative injury in adrenal glands.…”

“…Thus, we speculate that the different medication strategy may have influenced the effect of resveratrol on adrenocortical steroidogenesis. The adrenal steroidogenic cells are particularly vulnerable to oxidative stress due to their unique ultramicrostructure and function [7]. In the adrenocortical cells, excessive amounts of molecular oxygen are used not only for aerobic energy production (ATP synthesis) in mitochondria but also for steroid biosynthesis, which generates reactive oxygen species (ROS) such as oxygen-centered free radicals and peroxides as by-products of oxidative metabolism [7,14,15].…”

“…The adrenal steroidogenic cells are particularly vulnerable to oxidative stress due to their unique ultramicrostructure and function [7]. In the adrenocortical cells, excessive amounts of molecular oxygen are used not only for aerobic energy production (ATP synthesis) in mitochondria but also for steroid biosynthesis, which generates reactive oxygen species (ROS) such as oxygen-centered free radicals and peroxides as by-products of oxidative metabolism [7,14,15]. Moreover, since the adrenocortical cells contain a high content of unsaturated membrane lipids, lipid peroxidationmediated oxidative damage of cellular membranes can adversely affect cholesterol processing and steroidogenesis [7,14,15].…”

“…In the adrenocortical cells, excessive amounts of molecular oxygen are used not only for aerobic energy production (ATP synthesis) in mitochondria but also for steroid biosynthesis, which generates reactive oxygen species (ROS) such as oxygen-centered free radicals and peroxides as by-products of oxidative metabolism [7,14,15]. Moreover, since the adrenocortical cells contain a high content of unsaturated membrane lipids, lipid peroxidationmediated oxidative damage of cellular membranes can adversely affect cholesterol processing and steroidogenesis [7,14,15]. Our previous studies have shown that LPS treatment results in mitochondrial oxidative damage in the adrenal gland, which probably leads to the decline of corticosterone responsiveness to exogenous ACTH [14,15].…”

NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects

“…At present, in humans, NNT mutations are known to be associated with adrenal insufficiency. Additionally, relationships between decreased NNT activity, modified mitochondrial redox regulation and cardiac failure have been recently reported (24,25,26).…”