Primary structure and organ-specific expression of the rat aryl hydrocarbon receptor repressor gene

Abstract

The aryl hydrocarbon receptor repressor (AhRR) is a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, providing a negative feedback loop with a xenobiotic or endogenous ligand-dependent signal transduction mediated by the AhR. We sequenced full-length AhRR mRNA extracted from the heart of a male Wistar rat injected intraperitoneally with 3-methylcholanthrene (3-MC) 24 h before. The 95.6 kb-long AhRR genome was clarified to consist of 11 exons and 10 introns. The constitutive expression of AhRR mRNA was prominent in males when compared with females in parallel with the sexual difference in AhR expression. Although AhRR was ubiquitously expressed in all tissues tested, the levels of AhRR expression were higher in the small intestine, where the 3-MC-dependent induction of CYP1A1 transcription was less significant, than in the heart, lung, liver, and kidney. The dose-dependent suppression of AhR-dependent transcriptional activation in both the presence and absence of 3-MC was observed in rat liver-derived RL-34 cells transiently transfected with the expression plasmid for AhRR in combination with the reporter plasmid. © 2006 Pharmaceutical Society of Japan.