Bimodal expression of CYP2D16 in the guinea pig adrenal cortex

Prior studies revealed an apparent bimodal distribution of adrenal xenobiot ic-metabolizing activities in outbred guinea pigs. High activities were cha racteristic of most animals but a minority had very low rates of metabolism . The present studies were done to determine the basis for this distributio n. Among the enzymatic activities abundant in guinea pig adrenal microsomes is bufuralol 1'-hydroxylation, a marker for CYP2D isozymes. Western blot a nalyses revealed that adrenal expression of CYP2D16, the guinea pig CYP2D a nalogue, was highly correlated with xenobiotic-metabolizing activities. Of 12 animals studied, 4 had low levels of adrenal CYP2D16 expression and corr espondingly low bufuralol 1'-hydroxylase and benzphetamine N-demethylase ac tivities. In contrast, adrenal expression of steroidogenic P450 isozymes (C YP17 and CYP21) and the corresponding steroid hydroxylase activities were s imilar in all animals. There was also no evidence of polymorphism in hepati c xenobiotic metabolism. The results suggest that the bimodal expression of adrenal CVP2D16 is at least partly responsible for the variability in adre nal xenobiotic metabolism, and that this pattern of expression is not appli cable to other adrenal P450 isozymes or to hepatic CVP2D16. Further studies are needed to determine if genetic polymorphism is responsible for the mod e of adrenal CVP2D16 expression. Copyright (C) 2000 S. Karger AG, Basel.