Induction of synthesis of bovine adrenocortical cytochromes P-450 scc, P-450 11 β, P-450 c21, and adrenodoxin by prostaglandins E 2 and F 2α and cholera toxin

Abstract

To further elucidate the mechanisms by which ACTH (adrenocorticotropin) exerts its long-term action to maintain normal levels of adrenocortical cytochromes P-450 and related enzymes, the abilities of cholera toxin and prostaglandins E 2 and F 2α to induce the synthesis of cytochromes P-450 scc, P-450 11 β , and P-450 c21 and adrenodoxin have been examined. These effectors stimulate the production of cyclic AMP and thus steroidogenesis in the adrenal cortex. Using bovine adrenocortical cells in primary monolayer culture, we have shown that treatment with cholera toxin results in increased synthesis of cytochromes P-450 scc and P-450 11 β and adrenodoxin, similar to the effect observed upon ACTH treatment. Prostaglandins E 2 and F 2α are less effective at inducing the synthesis of the mitochondrial cytochromes P-450, and do not seem to induce the synthesis of adrenodoxin. Furthermore, cholera toxin was found to be less effective at inducing the synthesis of microsomal cytochrome P-450 c21 than ACTH, and no more effective than the prostaglandins. Thus, while it appears that elevation of cyclic AMP levels is a necessary step leading to increased synthesis of adrenocortical forms of cytochrome P-450, the detailed mechanism of this induction will be found to be different for each of the different enzymes.