Effects of microsomal enzyme inducers on thyroid follicular cell proliferation and thyroid hormone metabolism

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 nor increase serum TSH-that is. 3-methylcholanthrene (3MC) and Aroclor 1254 (PCB)-do nor increase thyroid follicular cell proliferation. Deiodination does not appear to be the reason why serum T-3 concentrations are maintained in microsomal enzyme inducer-treated rats. We have also shown that those microsomal enzyme inducers that increase serum TSH increase T-3 UDP-glucuronosyltransferase (UGT) activity, whereas those microsomal enzyme inducers that do not increase serum TSH do not increase T-3 UGT activity. This finding suggests that induction of T-3 glucuronidation, rather than T-4 glucuronidation, mediates increases in serum TSH of microsomal enzyme inducer treated rats.