L-triiodothyronine (T₃) regulates cellular growth rate, growth hormone production, and levels of nuclear T₃ receptors via distinct dose-response ranges in cultured GC cells

Cultured rat somatotrophic cells have been useful models for the study of thyroid hormone action. A consensus of previous reports has indicated that approximately 0.2 nM T₃ results in 50% occupancy of T₃ nuclear receptors as well as halfmaximal stimulation of several T₃ responses. To characterize the nature of thyroid hormone responses in GC cells, we studied in detail the T₃ dose relationships between nuclear receptor occupancy and three thyroid hormone responses (cell growth, GH production, and T₃ nuclear receptor regulation). The dose response to T₃ for each parameter was unique, and none was identical to the dose response for receptor occupancy. Respective T₃ concentrations and percentage of T₃ nuclear receptor occupancy resulting in 50% of the maximal response for GC cell growth were 0.05 ± 0.02 nM and 15 ± 3% (four experiments), 0.15 ± 0.04 nM and 27 ± 3% for GH production (three experiments), and 2.1 nM and 69% for down-regulation of T₃ nuclear receptors (two experiments). We conclude that the dose response for occupancy of the T₃ nuclear receptor covers a wide range of T₃ concentrations. Within the wide dose-response range for nuclear occupancy a spectrum of biological responses are regulated by distinct thyroid hormone dose ranges. These data suggest that the impact of T₃ nuclear receptor occupancy on T₃ responses might be variable and that the mechanisms involved may be clarified through studies in GC cells.