BPA metabolites to blame for endocrine disruption?

A new study from the University of California, San Diego (UCSD) School of Medicine has piled on more concerns about the effects of bisphenol A (BPA) on the human body after it has been ingested (PLOS One, October 4, 2012).

Of particular concern is the connection between BPA exposure and the disruption of estrogen signaling. Because BPA's molecular structure is similar to estradiol, it may bind to estrogen receptors. These receptors, which latch onto and hold estradiol and related estrogens, can also grab disparate chemicals. This can cause problems in the endocrine or hormone system, the researchers noted. Fetuses, infants, and young children are particularly prone to being affected.

According to Michael E. Baker, PhD, a UCSD professor of medicine, and Charlie Chandsawangbhuwana, a graduate student in the UCSD Department of Bioengineering, several research labs have reported that BPA binds weakly to the estrogen receptor, suggesting that something else is interacting with this receptor.

Three-dimensional modeling performed by the researchers revealed that one of the molecules that results from BPA being metabolized (MBP) binds more effectively to estrogen receptors than BPA. MBP has a 100- 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 when it was discovered in 2004 by Shin'ichi Yoshihara, PhD, and colleagues at Hiroshima International University.

In their PLOS One study, Baker and Chandsawangbhuwana revived Yoshihara's research. 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 3D modeling supports the concept that BPA is not the cause of endocrine disruption; rather, MBP and/or several BPA metabolites are likely to blame, according to Baker.

He said the 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.

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