NTP identifies endocrine-disrupting chemicals in Tox21 screen
National Toxicology Program (NTP) researchers collaborated with scientists across the country to screen approximately 10,000 chemicals for whether they activated estrogen-related receptor alpha (ERR-alpha), a nuclear receptor involved in numerous biological processes. The work used high-throughput techniques to search the Tox21 database and is the first comprehensive analysis of potential endocrine disruptors that affect ERR-alpha signaling. Endocrine disruptors are compounds that mimic the body’s hormones and interfere with normal hormonal communication and signaling throughout the body.
ERR-alpha is expressed at high levels in metabolically active tissues and plays a role in maintaining energy homeostasis in response to environmental cues. In certain types of breast and prostate cancers, increased expression of ERR-alpha can lead to worsened outcomes. Therefore, the scientists wanted to understand which chemicals might affect ERR-alpha activity, thereby impacting health and disease.
The scientists used genetically modified human embryonic kidney cell lines to evaluate which chemicals activated ERR-alpha. They found more than five clusters of agonists, which are molecules that initiate a biochemical response. One of the chemical clusters was structurally similar to statins, a group of pharmaceutical compounds that remove fat from the bloodstream. The authors say that additional studies will be necessary to determine the full effects of statins on ERR-alpha activity. (KS)
Citation: Lynch C, Zhao J, Huang R, Kanaya N, Bernal L, Hsieh JH, Auerbach SS, Witt KL, Merrick BA, Chen S, Teng CT, Xia M. 2018. Identification of estrogen-related receptor alpha agonists in the Tox21 compound library. Endocrinology 159(2):744−753.