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 differently. In addition, dibutyryl cAMP-stimulated 20DHP secretion was unaffected by
CdCl2, while the site of the unstimulated effect was indirectly shown to involve steps between endogenous
cholesterol utilization and
20-hydroxycholesterol association with mitochondrial
cytochrome P450 side-chain cleavage
enzyme. In the present study we determined
CdCl2 effects on plasma membrane sites preceding pre-
dbcAMP-stimulation of 20DHP secretion. Y-1 cells were incubated 0.5 h in medium with or without
cadmium (using the concentration that inhibited
adrenocorticotropin- (
ACTH)-stimulated
steroid secretion by 50%) together with exogenously added maximally stimulating concentrations of
ACTH,
cholera toxin,
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 pathway.
Cadmium effects on
ACTH-stimulated endogenous cAMP secretion were also examined.
CdCl2 significantly reduced Y-1 cell 20DHP secretion following 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
cholesterol uptake by mitochondria as a consequence.