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

The effects of microsomal enzyme inducers on thyroid hormone homeostasis an d the thyroid gland are of concern. We have investigated the effects of mic rosomal enzyme inducers on thyroid follicular cell proliferation and thyroi d hormone metabolism in rats. We have shown that small increases in serum T SH 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)-i ncrease thyroid follicular cell proliferation, whereas those microsomal enz yme inducers that do nor increase serum TSH-that is. 3-methylcholanthrene ( 3MC) and Aroclor 1254 (PCB)-do nor increase thyroid follicular cell prolife ration. Deiodination does not appear to be the reason why serum T-3 concent rations are maintained in microsomal enzyme inducer-treated rats. We have a lso shown that those microsomal enzyme inducers that increase serum TSH inc rease T-3 UDP-glucuronosyltransferase (UGT) activity, whereas those microso mal enzyme inducers that do not increase serum TSH do not increase T-3 UGT activity. This finding suggests that induction of T-3 glucuronidation, rath er than T-4 glucuronidation, mediates increases in serum TSH of microsomal enzyme inducer treated rats.