Differential effects of polychlorinated biphenyl congeners on serum thyroid hormone levels in rats.
Polychlorinated biphenyls (PCBs) are known to reduce serum thyroxine (T(4)) in rats, but the relative effects of individual PCB congeners on thyroid hormones are not known. Thus, male Sprague-Dawley rats were administered Aroclor 1254, Aroclor 1242 (4, 8, 16, or 32 mg/kg/day), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 99 (2,2',4,4',5-pentachlorobiphenyl), PCB 118 (2,3',4,4',5-pentachlorobiphenyl) (2, 4, 8, or 16 mg/kg/day), PCB 126 (3,3'4,4',5-pentachlorobiphenyl) (2.5, 5, 10, 20, or 40 microg/kg/day), TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) (0.14, 0.43, 1.3, or 3.9 microg/kg/day), or corn oil via oral gavage for 7 days. Rats were necropsied 24 h after the last dose. Serum thyroid hormone levels were evaluated by radioimmunoassay, and induction of hepatic Cyp1a (a TCDD-inducible protein) and Cyp2b (a phenobarbital [PB]-inducible protein) activity was determined by ethoxyresorufin-O-deethylase and pentoxyresorufin-O-deethylase assays, respectively. Significant increases in Cyp1a activity occurred in response to PCBs, except PCB 95 and PCB 99. Aroclor 1254, PCB 99, and PCB 118 significantly induced Cyp2b activity. Serum total T(4) and free T(4) were dramatically reduced in response to each of the seven treatments in a dose-dependent manner. The marked T(4) reductions occurred in response to Aroclor 1254, PCB 99 (a PB-type congener), and PCB 118 (a mixed-type congener). In contrast, reductions in serum triiodothyronine (total and free) were variable and mild, and serum thyroid-stimulating hormone was not significantly affected by any of the compounds. These data indicate that the PB and mixed-type PCB congeners are more effective than the TCDD-type PCB congeners at reducing serum T(4).
Martin
Lori
L
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Klaassen
Curtis D
CD
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood*
D013963:Thyroid Hormones; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls