Differential Effects of Polychlorinated Biphenyl Congeners on Serum Thyroid Hormone Levels in Rats

Abstract

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).

Thyroid endocrine system disruption by pentachlorophenol: An in vitro and in vivo assay

“…PCP decreased the plasma T4 levels in rats (BruckerDavis, 1998;Kawaguchi et al, 2008). Decreased T4 levels are frequently observed in mammals, amphibian and fish models exposed to TH endocrine disruptors, e.g., PBDEs (Tomy et al, 2004;Ellis-Hutchings et al, 2006;Lema et al, 2008;Yu et al, 2010), PCBs (Donahue et al, 2004;Martin and Klaassen, 2010;Schnitzler et al, 2011), and perchlorates (Mukhi and Patino, 2007;Opitz et al, 2009;Schmidt et al, 2012). Decreased TT4 and increased TT3 levels and the consequent increased ratio of T3/T4 are frequently observed in fish exposed to TH endocrine disruptors (Chen et al, 2012;Wang et al, 2013).…”

Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

“…However, we were surprised that only the PCB congeners with TCDD-like activity, namely PCB-118 and PCB-126, significantly increased the biliary excretion of T 4 -glucuronide in vivo, whereas the PB-type congeners, PCB-95 and PCB-99, did not. We have shown that PCB-118 and PCB-126 significantly increased CYP1A2 activity [as quantified by ethoxyresorufin-O-deethylase (EROD) activity], whereas PCB-95 and PCB-99 increased CYP1B2 activity [as quantified by pentoxyresorufin-O-deethylase (PROD) activity] (Martin and Klaassen, 2010).…”

“…It is conceivable that PCB-99, PCB-118, and Aroclor-1254, which have PB-like activity (induction of CYP2B) (Martin and Klaassen, 2010), may also induce Oatp1a4 and increase hepatic uptake of T 4 . In fact, it has been shown that Oatp1a4 protein was increased 130% by PCB-99 but was decreased 72% by PCB-126 (Guo et al, 2002).…”

“…Rats (six per group) were administered the corn oil solutions of Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 g/kg per day), or TCDD (3.9 g/kg per day) via gavage for 7 consecutive days at a dose volume of 5 ml/kg. The dose selection was based on our dose-response studies of these PCBs (Martin and Klaassen, 2010). Control rats were administered corn oil (5 ml/kg).…”

“…We have previously shown that individual PCB congeners differentially reduce serum T 4 levels, with the PB-type and mixed-type PCBs being most effective (Martin and Klaassen, 2010). However, little is known about their ability to affect biliary excretion of T 4 -glucuronide.…”