Receptor affinity and biological potency of thyroid hormones in thyrotropic cells.
The nuclear receptor affinity for L-triiodothyronine (L-T3), L-thyroxine (L-T4), L-triiodothyroacetic acid (triac), and D-triiodothyronine (D-T3) was compared to the potency of these thyroid hormone analogues in regulating thyrotropin (TSH) production and the number of membrane receptors for thyrotropin-releasing hormone (TRH) in mouse thyrotropic tumor cells in culture. L-T3 and triac were equally potent and D-T3 was one-sixth to one-fifth as potent in binding to the receptor and in regulating TSH production and TRH receptor number. L-T4 was the least potent analogue in each instance, but its relative receptor-binding affinity, measured after 3 h, was significantly less than its somewhat variable relative biological potency, measured after 48 h. The cells were shown to monodeiodinate L-[125I]T4 to L-[125I]T3 in a time-dependent manner, and the enhanced biological potency of L-T4 was ascribed to its conversion to L-T3. Thyroid hormones appear to regulate TSH production and the number of receptors for TRH in thyrotropic cells in culture through interaction with a nuclear receptor.
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000096:biosynthesis*; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine / Q000031:analogs & derivatives / Q000494:pharmacology; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000494:pharmacology
D011956:Receptors, Cell Surface; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine