CBS and CSE Are Critical for Maintenance of Mitochondrial Function and Glucocorticoid Production in Adrenal Cortex

Abstract

Endogenous H₂S plays a critical role in the maintenance of mitochondrial function in the adrenal cortex, thereby resulting in an adequate adrenocortical response to ACTH.

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

“…The plasma corticosterone response to exogenous ACTH (Sigma-Aldrich) was determined as described previously [14]. Dexamethasone (Sigma-Aldrich) dissolved in saline, was injected i.p.…”

“…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].…”

“…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]. In addition, oxidative stress has also been implicated in adrenocortical dysfunction associated with aging, metal toxicity, and side-effects of anesthetic agents such as etomidate [2,22,23].…”

GYY4137, a Novel Water-Soluble, H2S-Releasing Molecule

“…For example, injection of GYY4137 prior to LPS administration in the rat protects against the ensuing endotoxic shock both in terms of partially restoring the depressed blood pressure and with respect to inhibiting the generation of proinflammatory cytokines and NO (Li et al, 2009;Wang, Liu, et al, 2014). In addition, GYY4137 administered 18 h after intra-articular injection of Complete Freund's Adjuvant (CFA) in the mouse reduced paw swelling but when administered 1 h before CFA, GYY4137 increased swelling suggesting that the effect of this donor in this animal model critically depends on the stage of the inflammation.…”