Hornsby P J
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912.
Free Radic Biol Med. 1989;6(1):103-15. doi: 10.1016/0891-5849(89)90163-9.
Because steroids reach high concentrations within the adrenal cortex, effects of the direct interaction of steroids and cytochrome P450 enzymes are possible and may involve oxidative damage. Steroid pseudosubstrate effects studied in cultured adrenocortical cells show that these effects are probably not mediated by steroid receptors. Release of oxidants during pseudosubstrate interaction with cytochrome P450s may be responsible for loss of enzymatic activity observed; enzyme activity can be protected by cytochrome P450 inhibitors, antioxidants, and lowered oxygen concentration. There may be pathological effects of pseudosubstrates in the adrenal cortex. Cytochrome P450/pseudosubstrate effects could be involved in the aging and death of adrenocortical cells in vivo, and necrosis of the adrenal cortex due to excessive ACTH stimulation or due to the action of adrenolytic chemicals could result from damage by oxygen radicals originating from cytochrome P450s. The possible mechanism of damage to the adrenal cortex by the xenobiotics dimethylbenzanthracene, TCDD, 3-methylcholanthrene, and o', p'-DDD are reviewed.
由于类固醇在肾上腺皮质内可达到高浓度，类固醇与细胞色素P450酶直接相互作用的影响是可能存在的，且可能涉及氧化损伤。在培养的肾上腺皮质细胞中研究的类固醇假底物效应表明，这些效应可能不是由类固醇受体介导的。假底物与细胞色素P450相互作用期间氧化剂的释放可能是观察到的酶活性丧失的原因；细胞色素P450抑制剂、抗氧化剂和降低的氧浓度可保护酶活性。假底物在肾上腺皮质中可能存在病理效应。细胞色素P450/假底物效应可能与体内肾上腺皮质细胞的衰老和死亡有关，并且由于促肾上腺皮质激素过度刺激或肾上腺溶解化学物质的作用导致的肾上腺皮质坏死可能是由细胞色素P450产生的氧自由基损伤所致。本文综述了外源性物质二甲基苯并蒽、四氯二苯并二恶英、3-甲基胆蒽和邻，对'-滴滴滴对肾上腺皮质造成损伤的可能机制。
