FIG. 5.

Working model for the mechanism through which AHR activation blocks milk production in mammary epithelial cells. (Right) In the absence of AHR agonists, we propose ARNT signaling promotes milk production during lactogenic stimulation. (Left) In the presence of AHR agonists, AHR translocates to the nucleus and forms a heterodimer with ARNT. AHR/ARNT heterodimers bind XRE sequences to increase transcription of AHR target genes, including AHRR. Once induced, AHRR competes with AHR for interaction with ARNT and forms a transcriptionally repressive complex, which we propose inhibits expression of milk proteins. Dashed lines indicate aspects of the model proposed by these data. Abbreviations: AHR, aryl hydrocarbon receptor; ARNT, aryl hydrocarbon receptor nuclear translocator; AHRR, aryl hydrocarbon receptor repressor; XRE, xenobiotic-responsive elements.