ACUTE THYROID-HORMONE WITHDRAWAL RAPIDLY INCREASES THE THYROTROPIN-BETA AND ALPHA-SUBUNIT MESSENGER RIBONUCLEIC-ACIDS IN MOUSE THYROTROPIC TUMORS

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 thyrotroptic tumor TtT97 were injected daily with T3 (10 .mu.g/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 hypothryoid control concentrations on day 0, and rose 4-fold between days 1 and 2 and 20-fold by day 5 (P < 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 < 0.001). Tumor TSH.beta. and .alpha.-subunit mRNA levels were 5% and 52% (P < 0.01) of hypothryoid control levels on day 0. TSH.beta. mRNA levels rose nearly 9-fold between days 1 and 2 (P < 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 < 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.