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.
When added to intact GH4Cl 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 125I-T3 in the post-nuclear supernatant fraction of cells lysed with Triton X-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 microM cytochalasin b or 150 microM dansylcadaverine was reversible within 2 h of drug removal, and inhibition due to 150 microM 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.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001693:Biological Transport, Active; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002738:Chloroquine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine / Q000378:metabolism*
D000970:Antineoplastic Agents; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D003571:Cytochalasin B; D002738:Chloroquine; C008542:monodansylcadaverine; D002103:Cadaverine