Role of TSH in the changes in thyroidal metabolism of [35S]methimazole in phenobarbital and thyroxine-treated rats.

The effect of phenobarbital (PB) and/or thyroxine on the thyroidal accumulation and oxidation of [35S]methimazole (MMI) and serum TSH levels was studied in rats. PB treatment increased the accumulation of MMI and the serum TSH levels, but concurrent administration of T4 reversed these effects. It was concluded that increased TSH secretion in PB-treated animals was likely to be the major mechanism involved in the increased MMI accumulation. PB also increased the intrathyroidal oxidation of MMI to sulphate. However, in contrast to the PB effect on accumulation, concurrent T4 administration only partially reversed the effect on oxidation. The results suggested that the increased oxidation of MMI in PB-treated animals was due to a direct effect of PB or possibly a combination of this direct effect and the indirect TSH effect. Possible mechanisms postulated for a direct effect were thyroidal microsomal enzyme induction and/or changes in thyroidal protein binding of MMI.