STRAIN DIFFERENCES IN ADRENAL MICROSOMAL STEROID-METABOLISM IN GUINEA-PIGS

We recently reported that CYP2D16, a xenobiotic-metabolizing P450 isoz yme, was expressed at higher levels in adrenal microsomes from inbred Strain 13 guinea pigs than in those from outbred English Short Hair (E SH) animals. Studies were done to determine if there also were strain differences in adrenal microsomal steroid metabolism. In both inner (z ona reticularis) and outer (zona fasciculata plus zona glomerulosa) zo ne preparations of the adrenal cortex, 21-hydroxylase activities were greater in microsomes from ESH than from Strain 13 guinea pigs. By con trast, 17 alpha-hydroxylase activities were similar in the two strains . In both strains, 21-hydroxylase activities were greater in inner tha n outer zone microsomes, but the opposite was found for 17 alpha-hydro xylase activities (outer>inner). Northern and Western analyses reveale d higher levels of CYP21 mRNA and protein in adrenals from ESH than St rain 13 guinea pigs, but there were no strain differences in CYP17 mRN A or protein concentrations. Despite the zonal differences in adrenal 17 alpha-hydroxylase and 21-hydroxylase activities, CYP17 and CYP21 mR NA and protein levels were similar in the inner and outer zones within each strain of guinea pig. The results demonstrate strain differences in microsomal steroid metabolism that are explained by differences in CYP21 expression. By contrast, the zonal differences in steroid hydro xylase activities may be attributable to post-translational mechanisms . (C) 1998 Elsevier Science Ltd. All rights reserved.