Cell Cycle-dependent Expression of Thyroid Hormone Receptor- Is a Mechanism for Variable Hormone Sensitivity□D

Thyroid hormone receptors (TRs) are ligand-regulatable transcription factors. Currently, little is known about the expression of TRs or other nuclear hormone receptors during the cell cycle. We thus developed a stable expression system to express green fluorescent protein-TR in HeLa cells under tetracycline regulation, and studied TR expression during the cell cycle by laser scanning cytometry. Only 9–15% of the nonsynchronized cell population expressed TR because the majority of cells were in G1 phase and did not express detectable amounts of TR. However, when cells were synchronized in early S phase with hydroxyurea and then released, TR expression levels increased in a cell cycledependent manner and peaked to 30–40% cells expressing TR at late G2/M phase before declining to nonsynchronized levels. Moreover, we observed a direct correlation between transcriptional activity and TR expression during the cell cycle. Similar cell cycle-dependent findings also were observed for endogenous TR in rat pituitary GH3 cells. Last, cycloheximide studies demonstrated that the increase in TR expression was primarily due to increased translation. These novel observations of cell cycle-dependent expression of TR suggest that differential hormone sensitivity can occur during the cell cycle and may contribute to cell cycle progression during normal development and oncogenesis.