Complexing of DDT and o,p'DDD with adrenal cytochrome P-450 hydroxylating systems

The chlorinated hydrocarbon pesticides, DDT and o,p'DDD were examined to determine their influence on adrenocortical steroid biosynthesis. Steroid 11β- and 21-hydroxylation, and cholesterol side chain cleavage were inhibited to significant degrees when the pesticides were present in preparations of bovine adrenocortical mitochondrial or microsomal cytochrome P-450. Spectrophotometric studies show that spectra induced in bovine mitochondrial and microsomal cytochrome P-450 preparations closely resemble those induced in the same preparations by steroid substrates. The influence of these pesticides was also studied in adrenal glands from rats on diets containing small quantities of DDT. Steroid 11β-hydroxylation was markedly reduced in these studies as with in vitro studies with the partially purified bovine cytochrome P-450 system. The studies implicate an interaction between DDT or o,p'DDD and adrenocortical cytochrome P-450 which inhibits steroid hormone formation.