Atomic imaging reveals how flame retardants compete with estrogens in the body

Flame retardants mimic estradiols in the body, potentially causing havoc on natural endocrine homeostasis, according to new 3D x-ray crystallography research published online Aug. 19 in Environmental Health Perspectives.

Rajendrakumar A. Gosavi, PhD, a research fellow at the Laboratory of Structural Biology at the National Institute of Environmental Health Sciences (NIEHS), and colleagues employed crystallography to glean the atomic structure of flame retardants as they bind and inhibit sulfotransferase, an important enzyme that metabolizes estrogens.

There are hundreds of different types of flame retardants used ubiquitously in the manufacturing of furniture, building materials, electronics, automobiles and consumer goods. The implications of this binding are as yet unknown, but this interaction between flame retardants and sulfotransferase could potentially mean unmitigated estrogens flooding the body.   

“Flame retardants have been of general interest recently and we were trying to figure out whether these things would bind similarly to PCBs and estradiol and what we discovered is that they appear to bind in the same position as estradiol would bind, actually competing for the estradiol binding site,” said Lars Pedersen, PhD, staff scientist and collaborative x-ray crystallography group leader for NIEHS, in an interview with Molecular Imaging.

Although the brominated flame retardant in this study, tetrabromobisphenol A (TBBPA), is no longer produced in the U.S., it and its metabolite, tetrabromodiphenyl ether, or BDE-47, are still present in the environment. The NIH’s National Toxicology Program reported earlier this year that TBBPA was linked to cancer and this category of flame retardant has also been implicated in neuro-, immuno- and reproductive toxicity. Since brominated flame retardants like TBBPA were already chemicals of interest, researchers wanted to know if they had the same effect on estradiol binding with sulfotransferase that PCBs were found to have. They do.

“If you have high enough concentrations of this in your body, it could potentially inhibit the ability to sulfate estradiol in the body for regulating the concentrations of circulating estrodial,” explained Pederson. Further research is needed to understand the full impact of this mimicry and the subsequently high volume of functional circulating estrogens on human health.

Researchers conducted x-ray crystallography by taking the protein of interest and mixing it with the flame retardant and then crystalizing the complex. This was then exposed it to an x-ray beam and the resulting defraction pattern creates a 3-D structural model of the crystal complex. This research compounds previous reports of environmental pollutants like PCBs (polychlorinated biphenyls) that similarly compete for estradiol binding.

Researchers are hoping this and further study will inform the healthcare industry about potential toxicity and prompt manufacturing industries to produce safer products. The next step is to look at other categories of flame retardants and their metabolites to find out more about how these materials disrupt the endocrine system.