Linking toxic chemicals with malfunctioning hormone systems

Endocrine disrupting chemicals (EDCs) are mostly man-made chemicals found in various products such as pesticides and personal care products that are associated with interfering with the hormonal system of not only human beings, but also other terrestrial and aquatic animals resulting in adverse effects such as developmental and reproductive problems. The Environmental Protection Agency (EPA) developed ToxCast, a large-scale experiment using a battery of over 700high-throughput screening (HTS) assays, in 2007 with the purpose of developing methods to prioritize chemicals for further screening and testing to assist EPA programs such as Endocrine Disruptor Screening Program (EDSP).

The hypothalamic-pitutary-thyroid (HPT) axis, the system that regulates thyroid hormone production via negative feedback relationships between blood serum levels of thyroid hormones (T3 and T4) and thyroid stimulating hormone (TSH), is disrupted by chemicals found in the ToxCast's phase I database. A total of 24 chemicals decreased thyroxine (T4) level, the major hormone which is secreted from the thyroid gland. Of these 24 chemicals, 19 increased (TSH) level while 5 didn't alter the level of TSH. These 24 chemicals activated 242 assays in ToxCast.

Thyroid hormone alterations of Nonthyroidal illness syndrome (NTIS), a syndrome where serum levels of T4 decreases while TSH level remains unaltered, have been associated with increased inflammatory responses. Using the chemical by assay heat map that we generated utilizing ToxCast's database, we propose to identify the genes that were activated by the chemicals and determine whether there is a difference in activation of the identified genes between the groups of chemicals that exhibit different hormone effects in animals. This will provide support for (or against) the hypothesis that some chemicals can produce a NTIS like hormone profile by activating inflammatory responses.