Abstract

Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T₄) in rats, but little is known about their ability to affect biliary excretion of T₄. 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]T₄ was administered intravenously, and blood, bile, and urine samples were collected for quantifying [¹²⁵I]T₄ and in bile [¹²⁵I]T₄ metabolites. Serum T₄ 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]T₄. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T₄-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T₄. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T₄-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [¹²⁵I]T₄ from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T₄ in response to PCBs did not always correspond with UGT activity toward T₄ or with increased biliary excretion of T₄-glucuronide. The rapid disappearance of [¹²⁵I]T₄ from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T₄ is an additional mechanism by which PCBs may reduce serum T₄.