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RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDS, PCDFS AND PCBS
Citation:
DeVito, M J., D. Ross, AND K M. Crofton. RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDS, PCDFS AND PCBS. Presented at SOT, San Francisco, CA, March 25-29, 2001.
Description:
RELATIONSHIP BETWEEN HEPATIC MICROSOMAL THYROXINE GLUCURONIDATION AND TOTAL SERUM THYROXINE CONCENTRATIONS IN RATS TREATED WITH PCDDs, PCDFs AND PCBs. D G Ross, K M Crofton, M J DeVito, NHEERL, ORD, USEPA, RTP, NC.
Many PHAHs decrease thyroxine (T4), possibly due to induction of T4-glucuronidation. This study examined changes in serum thyroxine (T4) and hepatic microsomal T4-glucuronidation activity following exposure to three classes of PHAHs. The first class was dioxin-like and included 2,3,7,8-chlorine substituted PCDDs and PCDFs (TCDD, PCDD, TCDF, 1 PeCDF, 4-PeCDF) as well as PCB 126. The second class of chemicals consisted of dioxin-like PCBs that have actions in addition to their binding to the Ah receptor (PCBs 77, 105, 118 and 156). A third class of chemicals are the di-ortho substituted PCBs that have phenobarbital-like enzyme inducing properties (PCBs 138, 153 and 180). Female Long Evans rats (25 days old) were administered chemicals daily by oral gavage for 4 days and serum and livers were collected 24 hours after the final dose. Serum total T4 concentrations were determined. Livers microsomal fractions were isolated and T4-glucuronidation activity was determined. The administration of the PCDDs, PCDFs and PCB 126 resulted in dose-dependent decreases in serum T4 of approximately 50%. Dioxin-like PCBs with multiple mechanisms of action resulted in dose-dependent decreases in serum T4 of up to 80-90%. Non-dioxin-like PCBs decreased serum T4 up to 80-90%. All classes of chemicals examined resulted in the induction of hepatic T4-glucuronidation. PCDDs, PCDFs and all the dioxin-like PCBs induced T4-glucuronidation to similar levels (4-7 fold). The di-ortho PCBs with phenobarbital-like effects also induced hepatic microsomal T-4 glucuronidation (~ 2 fold), but not to the extent as the dioxin-like chemicals. There was no consistent relationship between the magnitude of decrease in T4 and the extent of hepatic T4-glucuronidation for the chemicals examined. This suggests that the T4-glucuronidation assay may not reflect the true amount of T4 glucuronidation in vivo or that other mechanisms may be involved. This abstract does not reflect USEPA policy