STRAIN DIFFERENCES IN ADRENAL CYP2D16 EXPRESSION IN GUINEA-PIGS - RELATIONSHIP TO XENOBIOTIC METABOLISM

Experiments were done to determine the mechanisms responsible for diff erences in adrenal microsomal xenobiotic metabolism between Strain 13 and English Short-Hair (ESH) guinea pigs. The rates of adrenal xenobio tic metabolism (bufuralol 1'/-hydroxylase, benzo[a]pyrene hydroxylase, benzphetamine N-demethylase) were 2-3 times greater in microsomes fro m the Strain 13 animals. In both strains, xenobiotic-metabolizing acti vities were far greater in the inner zone (zona reticularis) than in t he outer zones (zona fasciculata and zona glomerulosa) of the adrenal cortex. Northern blot analyses of total adrenal RNA with a CYP2D16 cDN A as the probe revealed significantly greater amounts of CYP2D16 mRNA in the Strain 13 guinea pigs. In addition, SDS-PAGE and Western blotti ng of adrenal microsomes demonstrated higher concentrations of CYP2D16 protein in Strain 13 than in ESH animals. Expression of CYP2D16 was p redominantly in the inner zone of the adrenal, coinciding with the maj or site of xenobiotic metabolism. The results demonstrated higher leve ls of expression of CYP2D16 in adrenal glands from Strain 13 than from ESH guinea pigs, which may account for the strain differences in adre nal xenobiotic metabolism. Strain 13 guinea pigs should serve as a goo d experimental model for further studies on the regulation of adrenal CYP2D16. Copyright (C) 1996 Elsevier Science Inc.