IN VITRO ADRENAL BIOACTIVATION AND EFFECTS ON STEROID METABOLISM OF DDT, PCBs AND THEIR METABOLITES IN THE GRAY SEAL (HALICHOERUS GRYPUS)

Article abstract of DOI:10.1002/etc.5620130609

The irreversible binding of the DDT metabolites o, p'-DDD<2-(2-chlorophenyl)-2(4-chlorophenyl)-1,1-dichloroethane> and MeSO2-DDE<3-methylsulfonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene>, as well as their potential to inhibit mitochondrial steroid 11β-hydroxylation in the gray seal adrenal gland, was studied. The adrenal bioactivated both o, p'-DDD and MeSO2 -DDE in vitro. The irreversible binding of o, p'-DDD was, however, 17 times higher than that of MeSO2- DDE. In both cases, the enzymes responsible for the activation resided primarily in mitochondria, and inhibitory effects of cytochrome P450 inhibitors (metyrapone and SKF 525A) and NADPH omission indicated mitochondrial P450 enzymes as responsible for the bioactivation. Forty-micromolar concentrations of o, p'-DDD and p, p'-DDT<2-(4-chlorophenyl)-2(4-chlorophenyl)-1,1,1-trichloroethane> inhibited 11β-hydroxylation of glucocorticoids (10μM) by approximately 25 percent. In contrast, none of the studied compounds - MeSO2-DDE, p, p'-DDE, some PCBs, and methylsulfonyl-PCBs (40 μM) - affected the mitochondrial 11β-hydroxylase activity. Bioactivation of environmental pollutants such as DDT and PCB metabolites and inhibition of P450 11β-hydroxylase are discussed as possible reasons for the generation of the adrenocortical hyperplasia observed in Baltic seals. - Keywords: DDT; DDD; Methylsulfonyl-DDE; Seal adrenal; 11β-Hydroxylase.