EVIDENCE FOR AN ACTIVE STEP IN THYROID HORMONE TRANSPORT TO NUCLEI: DRUG INHIBITION OF L-125I-TRIIODOTHYRONINE BINDING TO NUCLEAR RECEPTORS IN RAT PITUITARY TUMOR CELLS

Abstract

When added to intact GH₄C₁ or GH₃ cells, cytochalasin b, dansylcadaverine, and chloroquine inhibited the binding of L-¹²⁵I-triiodothyronine (T³) to nuclear receptors within 30 min. These drugs also reduced the amount of 5 I-T³ in the post-nuclear supernatant fraction of cells lysed with Triton χ-100. If ¹²⁵I-T³ was added before the drugs, ¹²⁵I-T³ that was already bound did not dissociate, but further binding was blocked. Inhibition due to 10 μM cytochalasin b or 150 yM dansylcadaverine was reversible within 2 h of drug removal, and inhibition due to 150 μM chloroquine was partially reversible. Drug inhibition was overcome as the T³ concentration was raised. These drugs did not significantly inhibit ¹²⁵I-T³ binding to isolated nuclei, and nuclei isolated from drug-treated cultures bound as much ¹²⁵I-T³ as control nuclei. The results suggest that thyroid hormones reach their nuclear binding sites by an active transport process which is inhibited by the drugs studied.