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 half-maximal 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.
Halperin
Y
Y
Department of Medicine, Montefiore Medical Center, Bronx, New York 10467.
Surks
M I
MI
Shapiro
L E
LE
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D013006:Growth Hormone / Q000096:biosynthesis*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014284:Triiodothyronine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013006:Growth Hormone