Pituitary cells respond to thyroid hormone by discrete, gene-specific pathways.
Type 1 iodothyronine deiodinase (D1) converts T4 to T3, the active thyroid hormone, by removal of the outer ring iodine. Previous studies in liver and thyroid cells have shown that T3 regulates Type 1 deiodinase (dio1) gene expression by a mechanism not requiring ongoing protein synthesis. For certain T3-regulated genes, such as rat GH, T3-induced transcription is blocked by protein synthesis inhibitors. Because the somatotrope tumor cell lines express both dio1 and GH, we compared these two positively T3-regulated genes to establish whether cycloheximide blockade of T3 effects is cell-type or gene specific. In these cells, the T3 stimulation of dio1 messenger RNA (mRNA) is not blocked by cycloheximide, whereas the T3 effect on GH mRNA synthesis is eliminated. Other differences between these two genes were also noted. Retinoic acid does not alter dio1 gene expression or the response to T3 but increases GH and synergizes with T3. Dexamethasone alone had no effect on dio1 mRNA but did enhance the effect of T3 on both dio1 and GH. These results point to distinct pathways for T3 induction of mRNA synthesis from different genes within the same cell.
Maia
A L
AL
Thyroid Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Harney
J W
JW
Larsen
P R
PR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007453:Iodide Peroxidase / Q000235:genetics*; D007700:Kinetics; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D014284:Triiodothyronine; D003609:Dactinomycin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014212:Tretinoin; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D003513:Cycloheximide; D000242:Cyclic AMP; D007453:Iodide Peroxidase; D015056:1-Methyl-3-isobutylxanthine