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 μmol/l, decreased the rate of T₃ entry in a dose-dependent manner and did not influence the T₃ exit rate. At 200 μmol/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.