Acute thyroid hormone withdrawal rapidly increases the thyrotropin beta and alpha-subunit messenger ribonucleic acids...

We have abruptly discontinued T3 administration to hypothyroid mice bearing thyrotropic tumors and measured increases in tumor steady state TSH subunit mRNA levels with time. Hypothyroid mice bearing the thyrotropic tumor TtT97 were injected daily with T3 (10 micrograms/100 g BW, ip, daily) for 10 days. Groups of mice (n = 3) were killed on the day of the last T3 injection (day 0) and 1, 2, 3, or 5 days after stopping T3 treatment. Plasma T3 concentrations fell to subnormal values between days 1 and 2 after stopping T3 treatment. Plasma TSH and total TSH subunit concentrations were 3% of untreated hypothyroid control concentrations on day 0, and rose 4-fold between days 1 and 2 and 20-fold by day 5 (P less than 0.01). Plasma total alpha-subunit concentrations were 28% of untreated hypothyroid control concentrations on day 0, rose to 158% of baseline values by day 2, and rose 3-fold by day 5 (P less than 0.001). Tumor TSH beta and alpha-subunit mRNA levels were 5% and 52% (P less than 0.01) of hypothyroid control levels on day 0. TSH beta mRNA levels rose nearly 9-fold between days 1 and 2 (P less than 0.01). alpha-Subunit mRNA levels rose to 135% of initial values by day 2 and to 144% of initial values by day 3 (P less than 0.05). Changes in tumor TSH subunit mRNA levels paralleled changes in plasma subunit glycoprotein concentrations. Increases in tumor subunit mRNA levels after abruptly stopping T3 treatment occurred rapidly, predominantly between 24-48 h after stopping T3, and TSH beta mRNA was considerably more responsive than alpha-subunit mRNA.