Vanadium inhibits ACTH-mediated but not cyclic AMP-dependent adrenal steroidogenesis

We have studied the effect of vanadium on steroidogenesis using dispersed cells from rat adrenals. It was found that when the cells were stimulated by ACTH both vanadate and vanadyl sulfate inhibited adrenal steroidogenesis. In contrast, when steroidogenesis was supported by cAMP analogues, no inhibition was observed. The inhibitory action of vanadium compounds was also seen when cholera toxin or forskolin was used as a stimulant instead of ACTH, indicating that vanadate does not act on the ACTH-receptor protein. When adrenal cells were stimulated by ACTH, cholera toxin- or forskolin-supported cAMP levels were diminished equally by vanadate. In addition, the mitochondrial steroid hydroxylation per se was not inhibited by vanadium compounds using either endogenous or exogenous steroid substrates. Based on these results, it is concluded that the site of inhibition by vanadium is located in the vicinity of the guanine nucleotide-binding protein and the catalytic unit of adenylate cyclase.