Influence of dietary zinc deficiency during development on hepatic CYP2C11, CYP2C12, CYP3A2, CYP3A9, and CYP3A18 expression in postpubertal male rats

The present study investigated the effect of dietary zinc deficiency during the developmental period on hepatic cytochrome P450 (CYP) expression in po stpubertal male rats. Twenty-one-day-old weanling male Wistar rats were ran domly assigned to one of the following dietary groups: zinc-adequate (31 mg zinc/kg diet); marginal zinc-deficient (3 mg zinc/kg diet); severe zinc-de ficient (I mg zinc/kg diet); or pair-fed control for either the marginal or severe zinc-deficient group. All rats were killed at 63 days of age. Compa red with the corresponding pair-fed controls, marginal zinc deficiency decr eased CYP2C11-mediated testosterone 2 alpha- and 16 alpha -hydroxylase acti vities by 43 and 42%, respectively, whereas severe zinc deficiency reduced each of these activities by approximately 60%. The decrease in CYP2C11 acti vity was accompanied by a reduction in CYP2C11 protein and mRNA levels, as assessed by immunoblot and reverse transcription-polymerase chain reaction (RT-PCR) assays, respectively. Additional RT-PCR analysis indicated that se vere zinc deficiency decreased CYP3A2 and CYP3A18 mRNA levels by 49 and 43% , respectively, whereas it increased CYP2C12 (253%) and CYP3A9 (238%) mRNA expression. Plasma testosterone concentration was decreased by 67% in the m arginal zinc-deficient group when compared with the corresponding pair-fed control group. By comparison, it was below the limit of quantification (0.2 ng/mL) in the severe zinc-deficient rats. Overall, these results indicate that dietary zinc deficiency during the developmental period feminized the hepatic gene expression of the sexually dimorphic CYP2C11, CYP3A2, CYP3A18, CYP2C12, and CYP3A9 in postpubertal male rats. (C) 2001 Elsevier Science I nc. All rights reserved.