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Characterization of the Uridine Diphosphate-Glucuronosyltransferase-Catalyzing Thyroid Hormone Glucuronidation in Man¹

Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland DD1 9SY; and Department of Internal Medicine III, Erasmus University Medical School, Rotterdam 3015 GE, The Netherlands

Address all correspondence and requests for reprints to: Karen A. B. Findlay, Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland DD1 9SY. E-mail: k.a.b.findlay{at}dundee.ac.uk

Increased thyroid hormone glucuronidation in rats caused by exposure to xenobiotics has stimulated a search for the individual uridine diphosphate-glucuronosyltransferases (UGTs) catalyzing this reaction in rats and man. Microsomal preparations from Crigler-Najjar liver, normal human liver, and kidney have been used to try to identify the UGT isoforms responsible for glucuronidation of the thyroid hormones. The predominant thyroid hormone released from the thyroid gland, T₄, and the inactive rT₃ are glucuronidated by cloned expressed bilirubin UGT1A1 and also phenol UGT1A9. Results from Crigler-Najjar microsomal samples indicate that UGT1A1 is the main contributor to thyroid hormone glucuronidation in the liver, with rT₃ being the preferential substrate. In kidney microsomes thyroid hormone glucuronidation is more complex, suggesting that more than just the UGT1A9 isoform may be involved. Bioactive T₃ is not significantly glucuronidated by these isoforms and other UGTs, and sulfotransferases may be involved.

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