Epigenetic links genetics and environment in shaping endocrine function. Some endocrine inputs regulate the epigenetic mechanism by interacting with histone-modifying enzymes; these enzymes, in turn, might potentiate hormone receptor activities. Growing evidences about an interplay among endocrine, environment and epigenetic suggest an involvement in the aetiology of many diseases, like neurological ones. We already demonstrated in vivo that a prenatal exposure to polychlorinated biphenyl mix (PCBm) modulate some epigenetic marks as well as endocrine systems. To better clarify the interplay environment-endocrine mechanisms-epigenetics, we evaluated in vitro the role of environment (PCBm) in the interaction between histone modifying enzymes (Jarid1b) and hormone signals (androgen receptor, AR). We found that PCBm alone induces AR transcriptional activity in a dose dependent way, but antagonizes DHT binding to AR. Jarid1b potentiates AR transcriptional activity, independently of ligand and of cell phenotype; AR nuclear translocation is influenced by the presence of both PCBm and Jarid1b. PCBm auto-down regulates AR expression and this negative feedback is potentiated by Jarid1b and depends on AR promoter length. Collectively, these data suggest that AR modulation exerted by PCBm might imply chromatin remodelling, possibly mediated by Jarid1b. A further clarification of AR-Jarid1b-PCB interaction might be important to identify new aspects of neurological diseases like autism.