title: 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.
authors.affiliation: Barts and the London School of Medicine and DentistryWilliam Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: R
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Barts and the London School of Medicine and DentistryWilliam Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Kowalczyk
authors.affiliation: Barts and the London School of Medicine and DentistryWilliam Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: E
authors.initials: E
authors.lastname: Meimaridou
authors.affiliation: Barts and the London School of Medicine and DentistryWilliam Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: H L
authors.initials: HL
authors.lastname: Storr
authors.affiliation: Barts and the London School of Medicine and DentistryWilliam Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK l.a.metherell@qmul.ac.uk.
authors.forename: L A
authors.initials: LA
authors.lastname: Metherell
mesh_terms: D000309:Adrenal Insufficiency / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species
keywords: adrenal insufficiency; oxidative stress; reactive oxygen species; steroidogenesis