Forage findings: expanding the definition of EDCs.

Endocrine-disrupting chemicals (EDCs) can derail hormone signaling pathways in vertebrates by interacting with estrogen receptors. These same receptors can also serve as unintended docking sites for phytoestrogens, weakly estrogenic chemicals produced by plants to deter herbivores, attract beneficial insects, and recruit symbiotic nitrogen-fixing soil bacteria. Now Jennifer E. Fox, currently of the Center for Ecology and Evolutionary Biology at the University of Oregon, and colleagues report that environmental EDCs and phytoestrogens also share the ability to influence phytoestrogen signaling systems in a manner parallel to EDCs' effects in vertebrates--evidence that these chemicals may have broader biological and ecological impacts than previously appreciated [EHP 112:672-677].

The team focused on the symbiosis between alfalfa and the soil bacterium Sinorhizobium meliloti. Alfalfa secretes luteolin and apigenin, phytoestrogens that attract and direct S. meliloti to infect the plant's roots, setting the stage for symbiosis. Luteolin also interacts with a bacterial receptor, nodulation D (NodD) transcriptional activator protein, and induces transcription of bacterial nod genes. These genes direct formation of root nodules, where S. meliloti draws carbon from the plant while providing it a useable source of nitrogen by converting atmospheric nitrogen to ammonia. Plants that have little or no nodulation do not thrive, and crop yields suffer.

The team examined whether EDCs that can bind to vertebrate estrogen receptors and interfere with normal hormone action would also influence luteolin--NodD receptor signaling. They added environmentally relevant concentrations of 62 natural and synthetic environmental EDCs to bacterial cultures, then assayed for receptor-controlled transcription. They also investigated whether NodD receptors bore a molecular resemblance to vertebrate estrogen receptors.

Of the 62 chemicals tested, 45 significantly inhibited nod gene activation and luteolin--NodD receptor signaling. The inhibitors represent a variety of chemical classes: organochlorine pesticides, herbicides, polyaromatic hydrocarbons, plastics by-products, polychlorinated biphenyls, hormone-active compounds such as diethylstilbestrol, and phytoestrogens produced by several plants. One chemical, bisphenol A, also induced nod gene expression, but only in the absence of luteolin. After comparing the amino acid sequences of NodD and estrogen receptors and the nucleotide sequences of their genes, the team did not find the two proteins to be similar.

Fox and colleagues conclude that EDCs do affect luteolin--NodD receptor signaling, which implies that the effects of these chemicals are not confined to vertebrates expressing estrogen receptors. They suggest that the current definition of endocrine disruption should be broadened to encompass unconventional environmental targets.