Thyroid hormones rapidly and stringently regulate the messenger RNA levels of the thyrotropin-releasing hormone (TRH) receptor and the TRH-degrading ectoenzyme.

The responsiveness of adenohypophyseal target cells for the hypothalamic neuropeptide TRH is known to change depending on the hormonal and physiological conditions of the organism. We describe here the effects of thyroid hormones on the transcript levels of the TRH receptor, the TRH-degrading ectoenzyme, and TSH in rat pituitary, as revealed by Northern blot analysis. After a single injection of T3 (30 micrograms/100 g BW), the transcript levels of the TRH receptor decreased transiently, reaching 35% of control values 4 h after injection, and returned to basal levels within 24 h. In contrast, the messenger RNA (mRNA) levels of the TRH-degrading ectoenzyme increased more dramatically in response to the same hormonal stimulus. Maximal levels (> 10 times above the control value) were present from 6-24 h after the injection, returning to basal values within 96 h. For both transcripts, the observed effects changed in a dose-dependent manner, but the mRNA levels of the TRH-degrading ectoenzyme were more tightly regulated. Under the experimental conditions used, the mRNA levels of PRL and GH were not affected by the application of T3, and those of alpha-subunit exhibited only minor reductions. The TSH beta transcripts however, decreased rapidly in length and slowly in concentration, finally reaching almost undetectable levels 48 h after the injection. Subsequently, newly synthesized TSH beta mRNA, the same size as the transcripts from euthyroid rats, could be detected 96 h after treatment with T3. Upon treatment of the animals with the mild goitrogenic agent n-propylthiouracil (200 mg/liter drinking water), a fast reduction in the transcript levels of the TRH-degrading ectoenzyme became evident. Within 1 day, mRNA levels decreased to less than 50% of control values. At this stage, no effects were observed on the transcript levels of either the TRH receptor or TSH beta. After 4 days of n-propylthiouracil treatment, the mRNA levels of the enzyme decreased further to 15% of control values, whereas the transcript concentrations of the TRH receptor and TSH beta rose by factors of 2 and 3.3, respectively. The extremely stringent regulation of the TRH-degrading ectoenzyme, a mirror image of that of the TRH receptor, strongly suggests that this enzyme represents an important regulatory element, controlling the stimulation of TRH target cells and, thus, adenohypophyseal hormone secretion.