HOOPFER, E.D.; DENVER, R.J.*: Synergistic Upregulation of Thyroid Hormone Receptor mRNAs by Thyroid Hormone and Corticosterone in Tadpoles of Xenopus laevis
Corticosteroids (CS) potentiate thyroid hormone (T3)-induced metamorphosis in several amphibian species. We tested the hypothesis that corticosterone (B) induces T3 receptor (TR) expression and that this effect is at the level of transcription. Tail explant cultures were initiated from St. 54 Xenopus tadpoles and treated for 7 days with or without T3 at 10 or 100 nM, B at 100, 500 or 3400 nM, or 10 nM T3 plus B at 100, 500 or 3400 nM. Tails were imaged daily, areas calculated and dry weights determined at the end of the experiment. Separate groups of similarly treated tails were harvested at 2 and 5 days after the initiation of hormone treatments and total RNA extracted for Northern blot analysis. T3 at 100 nM caused significant tail regression but 10 nM T3 alone did not. B alone caused a dose-dependent increase in final tail dry weight. All doses of B synergized with 10 nM T3 to cause tail regression comparable to the 100 nM T3 dose. At the two time points T3 alone caused a dose-dependent increase in TR-ALPHA and TR-BETA mRNAs. Interestingly, B alone also caused a dose-dependent increase in both TR mRNAs. T3 at 10 nM plus B produced a synergistic effect comparable to the level of gene induction caused by 100 nM T3. T3 caused a dose-dependent upregulation of glucocorticoid receptor (GR) mRNA but B had no effect. Xenopus TR-BETA promoter activity was upregulated by 100 nM B in transfected XTC-2 cells, suggesting a direct transcriptional action of the GR on TR-BETA expression. These results support the hypothesis that B synergizes with T3 to promote tail regression by upregulating TRs, most likely at the level of TR transcription. (Supported by NSF grant IBN9724080)
