Reference Type
Journal Article
Title
Effects of gestational and lactational exposure to coplanar polychlorinated biphenyl (PCB) congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone concentrations in weanling rats
Author(s)
Seo, BW; Li, MH; Hansen, LG; Moore, RW; Peterson, RE; Schantz, SL
Journal
Toxicology Letters ISSN: 0378-4274 EISSN: 1879-3169
Abstract
Perinatal exposure to polychlorinated biphenyl (PCB) mixtures or to certain ortho-substituted PCB congeners dramatically reduces circulating thyroxine (T4) concentrations. It is not clear whether perinatal exposure to coplanar PCBs or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a similar effect. In this study, time-mated Sprague-Dawley rats were dosed with 2 or 8 mg/kg/day PCB 77 (3,3',4,4'-tetrachlorobiphenyl), 0.25 or 1.00 micrograms/kg/day PCB 126 (3,3',4,4',5-pentachlorobiphenyl), 0.025 or 0.10 microgram/kg/day TCDD, or corn oil vehicle orally on gestation days 10-16. At weaning, plasma total T4 concentrations in PCB 77 and TCDD high-dose female pups were significantly depressed, but the changes were modest (84.4 and 79.6% of control, respectively). T4 concentrations in PCB 126 high-dose females and all high-dose males were also depressed slightly, but the changes were not statistically significant. UDP-Glucuronosyl transferase (UDP-GT) activity towards 4-nitrophenol was increased in all high-dose groups. Thus, the modest decreases in T4 could be due in part to increased T4 glucuronidation by UDP-GT. Triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were unchanged in all groups. In contrast to the minor changes in thyroid hormone status, liver microsomal ethoxyresorufin-O-deethylase (EROD) was markedly induced in all exposure groups and thymus weights were depressed in the high-dose groups. Because doses of coplanar PCBs or TCDD that caused marked induction of EROD activity had only minor effects on T4, we conclude that changes in thyroid hormone status at weaning are not among the more sensitive effects of perinatal exposure to these compounds.
Keywords
Administration, Oral; Animals; Animals, Suckling; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System/metabolism; Female; Glucuronosyltransferase/metabolism; Lactation; Male; Microsomes, Liver/drug effects/enzymology; Nitrophenols/administration & dosage/toxicity; Organ Size/drug effects; Oxidoreductases/metabolism; Polychlorinated Biphenyls/administration & dosage/metabolism/*toxicity; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Tetrachlorodibenzodioxin/administration & dosage/metabolism/*toxicity; Thymus Gland/drug effects; Thyroid Hormones/*blood
Mesh Terms
Administration, Oral Animals Animals, Suckling Cytochrome P-450 CYP1A1 Cytochrome P-450 Enzyme System Female Glucuronosyltransferase Lactation Male Microsomes, Liver Nitrophenols Organ Size Oxidoreductases Polychlorinated Biphenyls Pregnancy Random Allocation Rats Rats, Sprague-Dawley Tetrachlorodibenzodioxin Thymus Gland Thyroid Hormones