SAN DIEGO—Numerous studies have reported associations between bisphenol A (BPA) exposure and myriad adverse health and development effects, from cancer and neurological disorders to physiological defects and, perhaps, a cause of childhood obesity. Now, new research published in the journal PLoS ONE suggests metabolic changes that take place once BPA is broken down inside the human body pose a greater health threat than previously thought.
Of particular concern is that BPA exposure is correlated with disruption of estrogen signaling. The chemical’s molecular structure is similar to that of estradiol, one of the human body’s three main estrogens, suggesting that BPA binds to estrogen receptors. In binding to the estrogen receptor, BPA can disrupt the body’s endocrine or hormone system, with consequences especially worrisome for fetuses, infants and young children. Earlier this year,the U.S. Food and Drug Administration (FDA) banned BPA in baby bottles and sippy cups.
Scientists at UC San Diego School of Medicine said three-dimensional modeling suggests a metabolite of BPA—a molecule produced when BPA is metabolized or broken down by the body—actually binds to the estrogen receptor much more strongly than BPA itself. The finding could point the way to development of a new class of drugs designed to specifically inhibit excessive estrogen activity linked to disease.
In 2004, researchers in Japan discovered that another compound, dubbed MBP, was produced when BPA was metabolized. MBP has a 100-fold to 1,000-fold stronger bond to the estrogen receptor than BPA; however, the structural basis for MBP’s high affinity for the estrogen receptor was not investigated further.
For this study, the researchers creating 3D molecular models of MBP and BPA in the estrogen receptor and matching it against the crystal structure of estradiol in the estrogen receptor. They found that MBP’s longer structure allows both ends of the chemical to interact with the estrogen receptor in a way similar to estradiol. The shorter BPA molecule contacts the receptor at just one end, resulting in a weaker connection, providing an explanation for BPA’s lower affinity for the estrogen receptor.
The researchers said the 3D modeling supports the idea “that BPA is not the endocrine disruptor culprit. Instead, MBP is one (of perhaps several BPA metabolites) that causes disruption of estrogen signaling in humans and other animals."
They said research points to the need to measure MBP levels in urine and blood of patients suspected of BPA-mediated health effects, and may fuel development of a new therapeutic treatment for conditions linked to excessive estrogen levels and activity, such as some forms of breast and prostate cancers.