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4-Hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl-Mediated Decrease in Serum Thyroxine Level in Mice Occurs through Increase in Accumulation of Thyroxine in the Liver
- Source :
- Drug Metabolism and Disposition. 37:2095-2102
- Publication Year :
- 2009
- Publisher :
- American Society for Pharmacology & Experimental Therapeutics (ASPET), 2009.
-
Abstract
- 4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl (4-OH-CB187) was selected as a major hydroxylated polychlorinated biphenyl metabolite detected from serum of wildlife and humans and was examined for its effect on level of serum thyroid hormone in mice. Four days after treatment of C57BL/6 and DBA/2 mice with 4-OH-CB187 (1.0 mg/kg), the serum total thyroxine (T(4)) and free T(4) levels were decreased in both strains of mice. On the other hand, no significant changes in the level and activity of the T(4)-UDP-glucuronosyltransferases, including UGT1a and UGT1a1, by the 4-OH-CB187 treatment were observed in either strain of mice. No 4-OH-CB187-mediated change in level of serum thyroid-stimulating hormone was observed in either strain of mice. Binding levels of [(125)I]T(4) to serum proteins after administration of [(125)I]T(4) were significantly changed in 4-OH-CB187-pretreated mice: a decrease in the level of serum [(125)I]T(4)-transthyretin (TTR) complex and an increase in the binding level of [(125)I]T(4) to serum albumin and thyroxine binding protein in both strains of mice. Clearance from serum of T(4) was promoted by 4-OH-CB187 pretreatment in both C57BL/6 and DBA/2 mice, and the levels of T(4) in several tissues, especially the liver, were increased. In addition, 4-OH-CB187-mediated decreases in serum total T(4) and free T(4) levels were observed in wild-type and TTR-heterozygous mice but not in TTR-deficient mice. The present findings show that 4-OH-CB187 shows a definite ability to decrease serum T(4) level and further indicate that the 4-OH-CB187-induced decrease would occur through increase in accumulation of T(4) in the liver.
- Subjects :
- Male
Thyroid Hormones
medicine.medical_specialty
Ratón
Metabolite
Serum albumin
Pharmaceutical Science
Biology
Mice
chemistry.chemical_compound
Internal medicine
medicine
Animals
Tissue Distribution
Pharmacology
Thyroid
Blood Proteins
Polychlorinated Biphenyls
Blood proteins
Mice, Inbred C57BL
Thyroxine
Transthyretin
medicine.anatomical_structure
Endocrinology
Liver
chemistry
Mice, Inbred DBA
biology.protein
Female
Thyroxine-binding proteins
Hormone
Subjects
Details
- ISSN :
- 1521009X and 00909556
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Drug Metabolism and Disposition
- Accession number :
- edsair.doi.dedup.....a736bae441e871a776e021c87cdaa26d