Role of calcium channels in cadmium-induced disruption of cortisol synthesis in rainbow trout (Oncorhynchus mykiss)

The mechanisms of toxicity of cadmium (Cd2+) in adrenal steroidogenesis were investigated in vitro in adrenocortical cells of rainbow trout (Oncorhynchus mykiss). Toxicity of Cd2+ was increased in absence of extracellular Ca2+, but was prevented in Ca2+-supplemented medium. Pretreatment of cells with BAY K8644 (BAY), an agonist of voltage-dependent calcium channels, increased the Cd2+-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 Cd2+. These results suggest that opening of voltage-dependent calcium channels with BAY may allow Cd2+ entry at the same time as calcium, thus increasing toxicity of Cd2+, however voltage-dependent calcium channels may not be the only way of entry into adrenocortical cells. The influx of Cd2+, measured as intracellular Cd2+ using Fluo-3 in PREG-stimulated adrenocortical cells, was significantly enhanced by the stimulation. These results suggest that the deleterious effect of Cd2+ on cortisol steroidogenesis may be enhanced when the endocrine stress response is triggered.