Lacroix Alexandra, Hontela Alice
Département des Sciences Biologiques, Université du Québec à Montréal, TOXEN Research Centre, C.P. 8888 Succ. CentreVille, Montréal, Qc., Canada H3C 3P8.
Comp Biochem Physiol C Toxicol Pharmacol. 2006 Oct;144(2):141-7. doi: 10.1016/j.cbpc.2006.07.008. Epub 2006 Jul 21.
The mechanisms of toxicity of cadmium (Cd(2+)) in adrenal steroidogenesis were investigated in vitro in adrenocortical cells of rainbow trout (Oncorhynchus mykiss). Toxicity of Cd(2+) was increased in absence of extracellular Ca(2+), but was prevented in Ca(2+)-supplemented medium. Pretreatment of cells with BAY K8644 (BAY), an agonist of voltage-dependent calcium channels, increased the Cd(2+)-mediated inhibition of ACTH-stimulated secretion but not pregnenolone (PREG)-stimulated secretion. Nicardipine, an antagonist of voltage-dependent calcium channels, also increased the inhibition of adrenocorticotropic hormone (ACTH)-stimulated secretion by Cd(2+). These results suggest that opening of voltage-dependent calcium channels with BAY may allow Cd(2+) entry at the same time as calcium, thus increasing toxicity of Cd(2+), however voltage-dependent calcium channels may not be the only way of entry into adrenocortical cells. The influx of Cd(2+), measured as intracellular Cd(2+) using Fluo-3 in PREG-stimulated adrenocortical cells, was significantly enhanced by the stimulation. These results suggest that the deleterious effect of Cd(2+) on cortisol steroidogenesis may be enhanced when the endocrine stress response is triggered.
在虹鳟（Oncorhynchus mykiss）肾上腺皮质细胞中，对镉（Cd(2+)）在肾上腺类固醇生成中的毒性机制进行了体外研究。在无细胞外钙（Ca(2+)）的情况下，Cd(2+)的毒性增加，但在补充了Ca(2+)的培养基中则受到抑制。用电压依赖性钙通道激动剂BAY K8644（BAY）预处理细胞，增加了Cd(2+)介导的对促肾上腺皮质激素（ACTH）刺激分泌的抑制作用，但对孕烯醇酮（PREG）刺激的分泌没有影响。电压依赖性钙通道拮抗剂尼卡地平也增加了Cd(2+)对促肾上腺皮质激素（ACTH）刺激分泌的抑制作用。这些结果表明，用BAY打开电压依赖性钙通道可能会使Cd(2+)与钙同时进入，从而增加Cd(2+)的毒性，然而电压依赖性钙通道可能不是Cd(2+)进入肾上腺皮质细胞的唯一途径。在PREG刺激的肾上腺皮质细胞中，使用Fluo-3作为细胞内Cd(2+)测量的Cd(2+)流入量在刺激后显著增加。这些结果表明，当触发内分泌应激反应时，Cd(2+)对皮质醇类固醇生成的有害作用可能会增强。
