PITUITARY-CELLS RESPOND TO THYROID-HORMONE BY DISCRETE, GENE-SPECIFIC PATHWAYS

Type 1 iodothyronine deiodinase (D1) converts T-4 to T-3, the active thyroid hormone, by removal of the outer ring iodine. Previous studies in liver and thyroid cells have shown that T-3 regulates Type 1 deiodinase (diol) gene expression by a mechanism not requiring ongoing protein synthesis. For certain T-3-regulated genes, such as rat GH, T-3-induced transcription is blocked by protein synthesis inhibitors. Because the somatotrope tumor cell lines express both diol and GH, we compared these two positively T-3-regulated genes to establish whether cycloheximide blockade of T-3 effects is cell-type or gene specific. In these cells, the T-3 stimulation of dio1 messenger RNA (mRNA) is not blocked by cycloheximide, whereas the T-3 effect on GH mRNA synthesis is eliminated. Other differences between these two genes were also noted. Retinoic acid does not alter diol gene expression or the response to T-3 but increases GH and synergizes with T-3. Dexamethasone alone had no effect on diol mRNA but did enhance the effect of T-3 on both diol and GH. These results point to distinct pathways for T-3 induction of mRNA synthesis from different genes within the same cell.