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Toxicologic Pathology
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Effects of Microsomal Enzyme Inducers on Thyroid Follicular Cell Proliferation and Thyroid Hormone Metabolism

Curtis D. Klaassen

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160-7140

Alan M. Hood

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160-7140

The effects of microsomal enzyme inducers on thyroid hormone homeostasis and the thyroid gland are of concern. We have investigated the effects of microsomal enzyme inducers on thyroid follicular cell proliferation and thyroid hormone metabolism in rats. We have shown that small increases in serum TSH can result in large increases in thyroid follicular cell proliferation. Furthermore, only those microsomal enzyme inducers that increase serum TSH—that is, phenobarbital (PB) and pregnenolone-16{alpha}-carbonitrile (PCN)—increase thyroid follicular cell proliferation, whereas those microsomal enzyme inducers that do not increase serum TSH— that is, 3-methylcholanthrene (3MC) and Aroclor 1254 (PCB)—do not increase thyroid follicular cell proliferation. Deiodination does not appear to be the reason why serum T3 concentrations are maintained in microsomal enzyme inducer—treated rats. We have also shown that those microsomal enzyme inducers that increase serum TSH increase T3 UDP-glucuronosyltransferase (UGT) activity, whereas those microsomal enzyme inducers that do not increase serum TSH do not increase T3 UGT activity. This fi nding suggests that induction of T3 glucuronidation, rather than T4 glucuronidation, mediates increases in serum TSH of microsomal enzyme inducer treated rats.

Key Words: Phenobarbital • glucuronidation • deiodination • thyroid tumor promotion • thyroxine • thyroid-stimulating hormone • triiodothyronine

Toxicologic Pathology, Vol. 29, No. 1, 34-40 (2001)
DOI: 10.1080/019262301301418838
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