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IN VITRO METABOLISM OF THYROID HORMONES BY RECOMBINANT HUMAN UDP-GLUCORONOSYLTRANSFERASES AND SULFOTRANSFERASES
Citation:
RICHARDSON, V. AND M. J. DEVITO. IN VITRO METABOLISM OF THYROID HORMONES BY RECOMBINANT HUMAN UDP-GLUCORONOSYLTRANSFERASES AND SULFOTRANSFERASES . Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
This study compares the catalytic glucuronidation and sulfation of thyroxine (T4) and triiodothyronine (T3) using recombinant human UGTs and SULTs.
Description:
Endocrine disruptors can decrease thyroid hormone levels via the induction of hepatic uridinediphosphate-glucoronosyltransferases (UGTs) and sulfotransferases (SULTs). Due to their ability to catalyze glucuronidation and sulfation of hormones and xenobiotics, UGTs and SULTs play an important role in hormone catabolism and xenobiotic detoxification. However, it is unclear if induction of hepatic conjugation alone is responsible for the decrease in circulating thyroid hormones by xenobiotics. This study compares the catalytic glucuronidation and sulfation of thyroxine (T4) and triiodothyronine (T3) using recombinant human UGTs and SULTs. All UGTs examined catalyzed T4 glucuronidation, but UGT1A8, only found in the gastrointestinal tract, had an activity nearly 4-fold higher than the other UGT isoenzymes. T3 glucuronidation was also catalyzed by all UGTs examined, but activity levels were much lower than UGT-T4 activity. UGT1A8 and UGT2B4 catalyzed T3 glucuronidation with activity levels as much as 8-fold higher than some of the other UGT isoenzymes. All SULTs examined catalyzed T4 and T3 sulfation, but overall T3 sulfation activity was greater than T4 sulfation activity. T4 sulfation activity of SULT1E was as much as 180-fold higher than some of the other SULT isoenzymes examined whereas T3 sulfation activity of SULT1E was as much as 26-fold higher than other SULTs. These data suggest that certain UGT and SULT isoenzymes may be more involved in thyroid hormone metabolism than others. In addition, extrahepatic isoenzymes such as UGT1A8 may play key roles in decreasing circulating thyroid hormones (This is an abstract of a proposed presentation and does not necessarily reflect USEPA policy.