Disruption of androgen receptor activity by synthetic and dietary aryl hydrocarbon receptor ligands

Abstract

There is a growing concern that many of the environmental and dietary chemicals that are ingested by humans but have not been thoroughly tested for endocrine activity may pose a significant health threat. These chemicals may have the potential to mimic or antagonize hormone action, possibly through binding to steroid receptors and interfering with transcriptional activity. The prostate is highly sensitive to androgens and requires precise hormonal control to regulate its growth and function.Prostate cells express both androgen receptor and aryl hydrocarbon receptor (AhR) and cross‐talk between the two pathways may affect the function of the prostate cell. A number of methods were used to characterize the impact of dietary and environmental AhR ligands on androgen action in a prostate cancer‐derived cell line. Our in vitro cell culture‐based assay utilizes androgen‐responsive promoter constructs in conjunction with a luciferase reporter gene. These results combined with those from a binding assay indicate that several of the AhR ligands, including resveratrol, indole 3 carbinol, curcumin and hexachlorobenzene antagonize androgen‐initiated transcriptional activity without binding to the androgen receptor. Environmental and dietary compounds have been implicated in the rising incidence of prostate cancer and insight into the mechanisms of endocrine disruption will help to clarify their role.