EFFECT OF THYROID-HORMONE ON T-3-RECEPTOR MESSENGER-RNA LEVELS AND GROWTH OF THYROTROPIC TUMORS

Thyrotropic tumors (TtT97) contain mRNA transcripts for three T3-receptor (TR) isoforms, alpha1, beta1 and beta2, and a non-receptor alpha2-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). TRbeta1 mRNA increased 5- to 6-fold, while TRbeta2 mRNA decreased by 76%. TRalpha1 and the alpha2-variant decreased by 52% and 70%, respectively. Therefore, the tumors decreased their growth rate in response to T4 administration, and increased the ratio of TRbeta1 to TRbeta2 mRNA. This raises the intriguing possibility of a correlation between the relative abundance of the TRbeta isoforms and tumor growth.