Effect of thyroid hormone on T3-receptor mRNA levels and growth of thyrotropic tumors.

ABSTRACT

Thyrotropic tumors (TtT97) contain mRNA transcripts for three T3-receptor (TR) isoforms, alpha 1, beta 1 and beta 2, and a non-receptor alpha 2-variant. We administered T4 (5 mg/l of drinking water) for one month to TtT97-bearing mice, to examine its effect on tumor growth and tumor TR isoform steady-state mRNA levels. Baseline mice were killed at the start of the experiment, and placebo mice were maintained hypothyroid. The treated tumors were 30-35% smaller than the baseline tumors (p = NS), while the placebo tumors were 2- to 7-fold larger than the baseline tumors (p < 0.05). TR beta 1 mRNA increased 5- to 6-fold, while TR beta 2 mRNA decreased by 76%. TR alpha 1 and the alpha 2-variant decreased by 52% and 70%, respectively. Therefore, the tumors decreased their growth rate in response to T4 administration, and increased the ratio of TR beta 1 to TR beta 2 mRNA. This raises the intriguing possibility of a correlation between the relative abundance of the TR beta isoforms and tumor growth.