Regulation of theαand Thyrotropinβ-Subunit Messenger Ribonucleic Acids by Thyroid Hormones*

Publisher Website
Google Scholar
Abstract
The regulation of mRNAs encoding the .alpha.- and .beta.-subunits of TSH by thyroid hormones (T4 [thyroxine] and T3 [triiodothyronine]) in mouse thyrotropic tumors and pituitary glands. Hypothyroid male (LAF1) mice bearing thyrotropic tumor (TtT97) were injected daily with T4 for 0, 1, 5, 12 or 33 days. After day 33 plasma levels of TSH and free (unassociated) TSH .beta.-subunit were reduced to less than 1% of control levels; free .alpha.-subunit was reduced to 6% of control levels. Steady state levels of subunit mRNAs in extracts of the thyrotropic tissues were measured by blot hybridization analyses using mouse subunit-specific cloned cDNAs. Treatment of mice with T4 caused a rapid decline in the levels of tumor mRNAs for both .alpha. and TSH.beta.; after day 1, .alpha. and TSH.beta. mRNA levels decreased to 35% and 10% of control values, respectively. Levels of TSH.beta. mRNA were undetectable after 5 days of T4 treatment; levels of .alpha.-subunit remained at 30-35% of control levels even after day 33. In a separate experiment, TSH.beta. mRNA decreased to 42% of the control level (P < 0.05); .alpha.-subunit mRNA remained at 64% of the control level (P = not significant) 4 h after a single injection of T4. T3 also caused a rapid decrease in the levels of both subunit mRNAs in the anterior pituitary glands of hypothyroid mice, but the effect was more complete on TSH.beta. mRNA levels. Apparently, thyroid hormones have rapid suppressive effects on the levels of mRNAs encoding the subunits of mouse TSH in the thyrotrope. The suppressive effects of thyroid hormones occur more rapidly and are greater for TSH.beta. than .alpha.-subunit mRNA. The parallel changes observed in the subunit mRNA levels and the plasma subunit protein levels in animals treated with thyroid hormones suggest that the changes in the plasma levels of TSH and subunits may reflect effects of thyroid hormones on TSH gene expression in addition to effects on secretion.