MODULATION OF ADRENAL-CELL FUNCTIONS BY CADMIUM SALTS .3. SITES AFFECTED BY CDCL2 DURING STIMULATED STEROID-SYNTHESIS

In previous studies cadmium chloride (CdCl2) nonlethally inhibited Y-1 mouse adrenal tumor cell 20-dihydroxyprogesterone (20DHP) secretion, affecting unstimulated and stimulated steroidogenic pathway sites diff erently. In addition, dibutyryl cAMP-stimulated 20DHP secretion was un affected by CdCl2, while the site of the unstimulated effect was indir ectly shown to involve steps between endogenous cholesterol utilizatio n and 20-hydroxycholesterol association with mitochondrial cytochrome P450 side-chain cleavage enzyme. In the present study we determined Cd Cl2 effects on plasma membrane sites preceding pre-dbcAMP-stimulation of 20DHP secretion. Y-1 cells were incubated 0.5 h in medium with or w ithout cadmium (using the concentration that inhibited adrenocorticotr opin- (ACTH)-stimulated steroid secretion by 50%) together with exogen ously added maximally stimulating concentrations of ACTH, cholera toxi n, forskolin, or adenosine triphosphate. Cholera toxin, forskolin and ATP bypass specific plasma membrane sites involved in the synthesis of intracellular cAMP and activate the steroid hormone biosynthetic path way. Cadmium effects on ACTH-stimulated endogenous cAMP secretion were also examined. CdCl2 significantly reduced Y-1 cell 20DHP secretion f ollowing exposure to ACTH, cholera toxin, forskolin, and ATP; it also significantly decreased endogenous cAMP secretion into culture medium. These data may be interpreted to suggest that CdCl2 altered Y-1 cell regulation of adenyl cyclase activity, which reduced cAMP-activated ch olesterol uptake by mitochondria as a consequence.