In vitro metabolism of thyroxine by rat and human hepatocytes. (May 2014)

• Record Type: Journal Article
• Authors: Richardson, Vicki M.; Ferguson, Stephen S.; Sey, Yusupha M.; DeVito, Michael J.
• Is Part Of: Xenobiotica. Volume 44:Number 5(2014:May)
• Page Start: 391
• Page End: 403
• Publication Date: 2014-05
• Subjects: Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.3109/00498254.2013.847990
• Languages: English
• ISSNs: 0049-8254

Abstract

<abstract> <title>Abstract</title> <p>1. The liver metabolizes thyroxine (T<sub>4</sub>) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T<sub>4</sub> conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T<sub>4</sub>. The objective of this study was to compare the metabolism of T<sub>4</sub> in untreated and 2, 2′, 4, 4′, 5, 5′-hexachlorobiphenyl (PCB 153)-treated primary sandwich-cultured hepatocytes from rat (SCRH) and human (SCHH).</p> <p>2. Basal metabolite concentrations were 13 times higher in the medium of SCRH compared to SCHH. Metabolite distribution in the medium of SCRH versus SCHH was as follows: T<sub>4</sub>G, (91.6 versus 5.3%); T<sub>4</sub>S, (3.6 versus 4.4%) and T<sub>3</sub> + rT<sub>3</sub>, (4.9 versus 90.3%). PCB 153 induced T<sub>4</sub>G in the medium of SCRH and SCHH; however, T<sub>4</sub>S and T<sub>3</sub> + rT<sub>3</sub> were changed but to a much lesser degree.</p> <p>3. The results indicate that baseline T<sub>4</sub> glucuronidation is greater in SCRH compared to SCHH. These data also suggest that glucuronidation may be a more important pathway for T<sub>4</sub> metabolism in rats and deiodination may be a favored pathway in humans; however, with PCB 153 treatment these data support glucuronidation as a primary route of T<sub>4</sub> metabolism in both rat and humans.</p> </abstract>