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EFFECTS OF BDE-47 ON NUCLEAR RECEPTOR REGULATED GENES AND IMPLICATIONS FOR THYROID HORMONE DISRUPTION.
RICHARDSON, V., D. STASKAL, M. J. DEVITO, AND L. S. BIRNBAUM. EFFECTS OF BDE-47 ON NUCLEAR RECEPTOR REGULATED GENES AND IMPLICATIONS FOR THYROID HORMONE DISRUPTION. Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Previous studies have shown that exposure to polybrominated diphenyl ethers (PBDEs) can decrease thyroid hormone levels via the induction of hepatic uridinediphosphate-glucoronosyltransferase, (UGTs) which catalyze glucuronidation of T4 resulting in T4-glucuronide excretion. Based on their ability to catalyze glucuronidation of hormones and xenobiotics, UGTs play a key role in hormone homeostasis and xenobiotic detoxification, but it is not certain if hepatic glucuronidation alone is responsible for the thyroid hormone level effects. This study further examines the ability of BDE 47 to disrupt thyroid hormone levels and pairs these effects with BDE 47-induced effects on genes which may be involved in thyroid hormone homeostasis using quantitative real-time PCR. 65-day old female mice were orally administered 3, 10, or 100 mg/kg/day of BDE-47 for 4 days. Animals were sacrificed 24 hours after the final dose (day 5) and liver, kidney and, serum were collected for analysis. BDE-47 caused an 11% decrease at 3 and 10mg/kg and a 43% decrease at 100mg/kg in total T4 levels. BDE-47 had no effect on liver and kidney UGT1A1, UGT1A6, and UGT2B5 mRNA levels. Increases were seen in liver UGT1A7 mRNA levels at 10 and 100mg/kg, but no changes were seen in UGT1A7 mRNA levels in kidney. The data shows increases in UGT1A7 mRNA levels with accompanying decreases in T4 levels at 10 and 100mg/kg, but no correlating increase in UGT1A7 with the T4 decrease at 3mg/kg. This suggests that inductions in UGTs could partly be responsible for decreased T4 levels, but other mechanisms may also be involved. (This is an abstract of a proposed presentation and does not necessarily reflect USEPA policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
EXPERIMENTAL TOXICOLOGY DIVISION