Altered thyroxin and retinoid metabolic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin in aryl hydrocarbon receptor-null mice

• Published in: Archives of toxicology Vol. 79; no. 5; pp. 260 - 267
• Main Authors: NISHIMURA, Noriko, YONEMOTO, Junzo, MIYABARA, Yuichi, FUJII-KURIYAMA, Yoshiaki, TOHYAMA, Chiharu
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.2005; Springer Nature B.V
• Subjects: Administration, Oral; Animals; Animals, Newborn; Biological and medical sciences; Cytochrome P-450 CYP1A1 - biosynthesis; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A2 - biosynthesis; Cytochrome P-450 CYP1A2 - genetics; Environmental Pollutants - toxicity; Enzyme Induction; Female; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation, Enzymologic - drug effects; Glucuronosyltransferase - biosynthesis; Glucuronosyltransferase - genetics; Homeostasis; Immunoenzyme Techniques; Liver - drug effects; Liver - enzymology; Male; Maternal Exposure; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Polychlorinated Dibenzodioxins - toxicity; Pregnancy; Receptors, Aryl Hydrocarbon - deficiency; Receptors, Aryl Hydrocarbon - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Rodents; Thyroid gland; Thyroxine - blood; Toxicology; Vitamin A - metabolism; Toxicity; Rodentia; Vitamin; Retinoid; Metabolism; Retinol; Aryl hydrocarbon receptor-null mice; Ah receptor; Vertebrata; Mammalia; Mouse; Animal; Retinoid ·Thyroxin ·2,3,7,8-Tetrachlorodibenzo- p-dioxin ·Vitamin A
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-004-0626-4

To determine whether the disruption of thyroid hormone and retinoid homeostasis that occurs after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be mediated by the arylhydrocarbon receptor (AhR), pregnant AhR-heterozygous (AhR+/-) mice were administered a single oral dose of 10 microg kg(-1) TCDD at gestation day 12.5. Serum and liver were collected on postnatal day 21 from vehicle-treated control or TCDD-treated AhR+/- and AhR-null (AhR-/-) mouse pups. Whereas TCDD exposure resulted in a marked reduction of total thyroxin (TT4) and free T4 (FT4) levels in the serum of AhR+/- mice, TCDD had no effects on AhR-/- mice. Gene expression of UDP-glucuronosyltransferase (UGT)1A6, cytochrome P450 (CYP)1A1, and CYP1A2 in the liver was induced markedly by TCDD in AhR+/- but not AhR-/- mice. Induction of CYP1A1 in response to TCDD was confirmed by immunohistochemical evidence in that CYP1A1 protein was conspicuously localized in the cytoplasm of hepatocytes in the centrilobular region. Levels of retinyl palmitate were greatly reduced in the liver of TCDD-exposed AhR+/- mice, but not in vehicle-treated AhR+/- mice. No effects of TCDD on retinoid levels in the liver were found in AhR-/- mice. We conclude that disruption of thyroid hormone and retinoid homeostasis is mediated entirely via AhR. Induction of UGT1A6 is thought to be responsible at least partly for reduced serum thyroid hormone levels in TCDD-exposed mice.