Persistent organic pollutants have dose and CAG repeat length dependent effects on androgen receptor activity in vitro

Recently, the effect of exposure to persistent organic pollutants (POPs) on sperm concentration was only seen in men with a short androgen receptor (AR) gene CAG repeat. In order to investigate whether these effects could be observed also in vitro, we tested the impact of 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4′-DDE) on 5α-dihydrotestosterone activated ARs containing 16, 22 and 28 CAG repeats, respectively. Single exposure to 4,4′-DDE had the most pronounced effect on the AR activity containing 16 CAG repeats, whereas 28 CAG was the most sensitive variant when a mixture of the two compounds was added. Thus, our in vitro results have confirmed the in vivo data indicating a CAG repeat length dependent effect of endocrine disrupters on the AR activity.

• The CAG repeat in the androgen receptor gene determines the effects of pollutants. • This finding confirmed previously reported epidemiological results. • The effect was seen at concentrations comparable to those found in exposed humans. • At higher levels, all androgen receptor variants were equally hampered in activity.