Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.
Level 5 - mechanism / opinion, no new human data
In vitro bench binding assay and SAR analysis without human clinical data
PubMed 14565775 · doi:10.1021/tx030011g
What was done
The authors developed and validated a low-cost, animal-free recombinant androgen receptor (AR) competitive binding assay, comparing its performance against prostate cytosol assays. They tested 202 natural, synthetic, and environmental chemicals across multiple structural classes (including steroids, bisphenol A derivatives, alkylphenols, parabens, phthalates, siloxanes, phytoestrogens, DDTs, PCBs, and organophosphates) and conducted structure-activity relationship (SAR) analyses using published ligand-AR crystal structures.
What was found
The abstract reports no numerical binding constants, IC50 values, or relative binding affinities. Qualitatively, hydrophobic interactions were identified as crucial for AR binding, and ligand interactions corresponding to the 3- and 17-positions of testosterone and R1881 were identified across different chemical classes.
Why it matters
This paper provides a large in vitro screening dataset to identify environmental chemicals that may act as endocrine disruptors via direct androgen receptor binding, establishing structural rules for predicting AR interactions.
Limits
The abstract reports no quantitative values for individual compounds. As a purely in vitro, cell-free competitive binding assay, it does not assess functional agonism versus antagonism, cellular bioavailability, metabolic activation or clearance, or in vivo endocrine toxicity.
Cited by
- supports Endocrine-disrupting chemicals interact directly with estrogen and androgen receptors, acting as anti-androgens or anti-estrogens by occupying receptor binding sites.