Polychlorinated biphenyl congeners that increase the glucuronidation and biliary excretion of thyroxine are distinct from the congeners that enhance the serum disappearance of thyroxine

L. A. Martin, D. T. Wilson, K. R. Reuhl, M. A. Gallo, Curtis D. Klaassen

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T 4) in rats, but little is known about their ability to affect biliary excretion of T 4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [ 125I]T 4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [ 125I]T 4 and in bile [ 125I]T 4 metabolites. Serum T 4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [ 125I]T 4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T 4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T 4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T 4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [ 125I]T 4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T 4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T 4-glucuronide. The rapid disappearance of [ 125I]T 4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T 4 is an additional mechanism by which PCBs may reduce serum T 4.

Original languageEnglish (US)
Pages (from-to)588-595
Number of pages8
JournalDrug Metabolism and Disposition
Volume40
Issue number3
DOIs
StatePublished - Mar 2012

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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