In vivo acute exposure to polychlorinated biphenyls: effects on free and total thyroxine in rats.
Hypothyroxinemia in rats has been well documented as a result of exposure to polychlorinated biphenyls (PCBs). Hypothetical mechanisms include induction of hepatic catabolic enzymes and cellular hormone transporters, and/or interference with plasma transport proteins. We hypothesized that if thyroxine displacement from transport proteins by PCBs occurs in vivo, it would result in increased free thyroxine (FT4). This study investigates the effects of a single oral dose of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153 at 60 mg/kg) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169 at 1 mg/kg) on rats at 28 or 76 days of age. Total thyroxine (TT4) and FT4 were measured at 0.5, 1, 2, 4, 8, 24, or 48 hours post-dosing. Microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD) activity and uridine diphosphoglucuronosyl transferase (UGT) activity were determined. No significant increase in TT4 or FT4 concentrations was seen at any time point. PCB 153 significantly decreased TT4 and FT4 in young and adult rats, with young rats showing a time-by-treatment interaction from 2 to 48 hours post-dosing in serum FT4. With PCB 169 exposure, young rats showed a decrease in FT4 only, whereas adult rats showed decreases in TT4 only. Hepatic EROD and PROD activities were both dramatically increased following PCB 169 and 153, respectively. Uridine diphosphoglucuronosyl transferase activity was increased only after PCB 169 exposure. These data demonstrate that neither PCB 153 nor PCB169 increased FT4, which supports the conclusion that these PCBs do not displace thyroxine from serum TTR, or if it does occur, there is no subsequent increase in serum FT4 in vivo.
Hedge
J M
JM
Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US EPA, Research Triangle Park, NC 27711, USA. hedge.joan@epa.gov
DeVito
M J
MJ
Crofton
K M
KM
D000284:Administration, Oral; D000375:Aging / Q000097:blood; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D013974:Thyroxine / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism
D052244:Endocrine Disruptors; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D013974:Thyroxine