A 30% solution of a polychlorinated biphenyl (PCB) mixture or a microscope immersion oil containing 34% PCB, when applied to the skin of rats, led to substantial increases in the biliary excretion of intravenously injected [125I]thyroxine (T4) in bile: plasma 125I ratios, in the biliary clearance rate of plasma [125I]T4, and in bile flow. Both PCB preparations also elevated liver weight, thyroid 125I uptake, and Sephadex uptake of [125I]triiodothyronine (T3), and depressed serum T4 concentrations; serum T3 levels were unaltered by the PCB solution or by the immersion oil containing PCB. PCB, either in mineral or immersion oil, reduced the free T4 index (serum T4 X fraction Sephadex T3 uptake), indicating a probable reduction in the concentration of free T4 in serum; the free T3 index, on the other hand, was elevated in PCB-treated rats. The same type of immersion oil, in which the PCB was replaced by a hydrogenated terphenyl, was without effect on any of the indices studied. Thus, the effects of microscope immersion oil on T4 metabolism were due to its PCB content. In thyroidectomized, T4-maintained rats, PCB in mineral oil again increased Sephadex uptake of [125I]T3, greatly reduced serum T4, and moderately reduced serum T3 levels; the free T4 index was substantially reduced and the free T3 index moderately lowered in treated animals. These data indicate that in PCB-treated rats both the peripheral conversion of T4 to T3 and thyroid T3 secretion were enhanced. The metabolic impact of thyroid hormone in PCB-treated animals was unchanged, as shown by normal activity of hepatic mitochondrial L-alpha-glycerophosphate dehydrogenase.
In rats four daily skin application of a 30% solution of a polychlorinated biphenyl (PCB) mixture in mineral oil or of a microscope immersion oil, containing 34% PCB, led to increases in liver weight, protein concentration of the 10 000 X g supernatant fluid of liver homogenates and the in vitro glucuronidation of thyroxine (T4) by the supernatant fluid, whether related to liver weight or to protein concentration in the reaction mixture. Similar effects occurred after feeding 250 ppm (mg/kg) of PCB in either Purina chow or a low-iodine diet for 11 days. It is concluded that increased hepatic T4 glucuronidation contributes to the enhanced biliary excretion of T4 previously observed in PCB-treated rats.
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