Effect of bisphenol A, tetrachlorobisphenol A and pentachlorophenol on the transcriptional activities of androgen receptor-mediated reporter gene

Previously, we developed an androgen receptor (AR)-mediated reporter gene assay system, and verified the antiandrogenic activity of bisphenol A (BPA) based on this assay. There were some similar phenol-ring structure chemicals which were widely used while little had been done to evaluate their effect to androgen. In the present study, we applied this assay to evaluate the androgenic and antiandrogenic activities of some phenolic chemicals including BPA, tetrachlorobisphenol A (TCBPA), and pentachlorophenol (PCP). The results showed that BPA exhibited potent antiandrogenic activity with IC50 value of 2.14 μM. TCBPA showed relative weaker activity with IC50 value of 10.45 μM and PCP did not show AR antagonistic activity. On the other hand, we failed to find AR agonistic effects of the three chemicals. To study the reason why BPA and TCBPA reduced the reporter gene expression, we increased the DHT concentration to 100 nM and 10 μM in the reporter assay. Then, we found that the antagonist activity of BPA and TCBPA decreased with the increase of concentration of DHT. This result indicated that these two test chemicals could compete with DHT for the binding of AR. When comparing the structure difference between BPA, TCBPA and PCP, we got a preliminary founding that 3,5-substituents of phenol ring of BPA decrease its antiandrogenic activity. These results provide some useful information for the assessment of the antiandrogenic activity of BPA like chemicals and the potential mechanism.