5,5'-Diphenylhydantoin decreases the entry of 3,5,3'-triiodo-L-thyronine but not L-thyroxine in cultured GH-producing cells.

We determined the effect of 5,5'-diphenylhydantoin (DPH) on the kinetics of T3 and T4 uptake in cultured GH-producing (GC) cells under serum-free conditions. GC cells accumulated [125I]T3 at a greater fractional rate than [125I]T4. The t 1/2 of exit of [125I]T4 and [125I]T3 previously equilibrated in GC cells was 28 min for T4 and 66 min for T3. T3 and T4 entry rates were not influenced by up to a 10,000-fold molar excess of nonradioactive T3, T4, d-T4, rT3, 3,5-T2 and diiodotyrosine. Thus, entry of T3 and T4 in GC cells appeared nonsaturable and was not influenced by various thyroid hormone analogues. DPH, 25-200 mumol/l, decreased the rate of T3 entry in a dose-dependent manner and did not influence the T3 exit rate. At 200 mumol/l DPH, T3 entry decreased by 40%. Rates of entry and exit of T4 were unaffected by DPH. DPH may affect T3 and T4 entry differentially at the level of the plasma membrane.