Emerging Research on Endocrine Disruptors
Schwartz, David A., Korach, Kenneth S., Environmental Health Perspectives
For more than three decades, the NIEHS has been one of the recognized leaders in the world in the study of endocrine disruptors, substances that mimic or alter hormonal effects in the body. In the 1970s, NIEHS scientists pioneered research on reproductive toxicity and discovered the hormonal toxicity of diethylstilbestrol (DES), a drug that for years had been prescribed to women to prevent miscarriage, but that was shown to later cause cancer and infertility in some of the children of these mothers. Clinical researchers used observations from this basic science to replicate in animal models what was being seen in patients, ultimately leading to the discontinued use of DES in pregnant women. Now NIEHS investigators are demonstrating that exposure to endocrine disruptors such as DES during critical developmental stages can actually reprogram the genomes of offspring to cause inappropriate gene expression, resulting in increased susceptibility later in life to diseases such as cancer, as well as to reproductive, metabolic, and developmental disorders. The ability of an environmental compound to induce an epigenetic disease state spanning several generations has significant implications for the study of disease origins and consequences of exposure. For this reason the study of endocrine disruptors continues to be a research priority at the NIEHS.
The NIEHS has been at the forefront of basic research to understand the toxicology of reproductive and developmental health. This is particularly important in the case of endocrine disruptors, which act by multiple mechanisms. To discern whether the toxicity of such chemicals is due to hormonal activity or some other activity of the compounds, researchers must first understand how estrogens and the estrogen receptor work at a basic level. Seminal work by NIEHS researchers has identified new sites of action and biological activities, developed animal models to show how estrogens work, and shown how environmental factors might disrupt them. Recent studies have found a contributing role for estrogen receptor signaling in the ovary with regards to ovulation, providing the potential for identifying its effect on subfertility or infertility.
Researchers in the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) have evaluated the endocrine-disrupting effects of seven phthalates, chemicals used in plastics manufacture, and the phytoestrogen genistein, found in soy. The phthalate evaluations have had broad impact, guiding regulatory agencies in making decisions on these chemicals. For example, the center's report was in part the basis of a Consumer Product Safety Commission recommendation that certain phthalates be removed from mouthing toys (such as teethers and rattles) due to concerns about children ingesting these chemicals. …