THE IMPACT OF CB-153 AND p,p-DDE ON ANDROGEN RECEPTOR FUNCTION
Reports regarding hampered male reproductive function due to exposure of exogenous agents have been published over the last decades. Agents of concern include persistent organohalogen pollutants (POP) that could modulate endocrine signalling pathways by interfering with natural hormones such as androgens or oestrogens by activation or inhibition of estrogen receptor and androgen receptor (AR) induced responses. All androgen actions are mediated through the AR, which contains a polymorphic glutamine repeat commonly referred to as the CAG repeat. High POP exposure in combination with a short CAG repeat (<20) has been associated with significantly lower sperm concentration. Our aim was to investigate if a mix of the two POP markers p,p-DDE and CB-153, could influence the AR activity in a CAG repeat length depending manner. The ability of three different CAG lengths (16, 22 and 28) to activate a reporter gene, together with 10 nM 5α-dihydrotestosterone (DHT), CB-153 and p,p-DDE was tested in vitro. In the presence of CB-153 and p,p-DDE, a median 26％ decreased activity was observed for AR CAG28 (p=0.03), as compared to AR CAG28 with no CB-153 and p,p-DDE added. This indicates that certain genotypes of the AR could be linked to a higher sensitivity to POP exposure.
Bj(o)rk C Nenonen H Giwercman A Bergman (A) Rylander L Lundberg Giwercman Y
Department of Clinical Sciences,Molecular Genetic Reproductive Medicine,Lund University,Malm(o),Swed Department of Clinical Sciences,Molecular Genetic Reproductive Medicine,Lund University,Malm(o),Swed Department of Environmental Chemistry,Stockholm University,Stockholm,Sweden Division of Occupational and Environmental Medicine,Lund University,Lund,Sweden
国际会议
北京
英文
1-4
2009-08-24（万方平台首次上网日期，不代表论文的发表时间）