Differential expression of CYP1A1 and CYP1A2, but not of ahr and arnt, in guinea pig adrenal and liver

• Published in: Endocrine research 1998, Vol.24 (3-4), p.631-632
• Main Authors: Black, Virginia H., Shaw, Peter M., Karchner, Sibel I., Powell, Wade, Hahn, Mark E.
• Format: Article
• Language: English
• ISSN: 0743-5800; 1532-4206
• DOI: 10.3109/07435809809032660

To test the relative induction of CYP1A1 and CYP1A2 in guinea pig adrenal and liver, the effects of 3,3′-methylcholanthrene (3MC), an archetypal inducer of CYP1A, were examined. RT-PCR analysis was performed using oligonucleotide primers corresponding to the 5′ and 3′ ends of the coding regions. PCR products of appropriate size (∼1.5kb) and sequence were obtained for CYP1A1 and CYP1A2 from both tissues; however, there were significant differences in the regulation of CYP1A expression in the liver vs adrenal. CYP1A1 mRNA was detectable in liver and adrenal of control guinea pigs and was induced in both tissues by 3MC, although levels were lower in the adrenal than in the liver. CYP1A2 mRNA was also present in both tissues of controls, but responded differently to 3MC in each. Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following 3MC treatment. To begin to define mechanisms responsible for this differential regulation we compared levels of expression of AHR and ARNT, two transcription factors involved in the induction of CYP1A by aromatic hydrocarbons such as 3MC. RT-PCR analysis was performed using degenerate oligonucleotide primers designed against AHR and ARNT sequences from highly conserved regions of the 5′ end of the bHLH or PAS domains and the 3′ ends of the PAS domains. PCR products of appropriate sizes were obtained from both tissues for AHR (∼ 600 bp) and ARNT (∼ 1 kb). Sequence analysis revealed high sequence identity with AHR1 and ARNT1, respectively, of other species. The mRNA for the two transcription factors was easily detectable and levels were similar in adrenal and liver tissue of control animals. Following 3MC treatment, ARNT, but not AHR, mRNA increased to the same extent in both tissues. The similarity in control and induced expression of AHR and ARNT in the two tissues suggests that other, tissue-specific, factors are involved in the differential regulation of CYP1A1 and CYP1A2 in the adrenal vs liver. (Supported by NIH DK39671, DK07421, HL 48476, ES00260, and ES07381).