EVIDENCE THAT THE MAJOR PHYSIOLOGICAL-ROLE OF TRH IN THE HYPOTHALAMICPARAVENTRICULAR NUCLEI MAY BE TO REGULATE THE SET-POINT FOR THYROID-HORMONE NEGATIVE FEEDBACK ON THE PITUITARY THYROTROPH

If a primary physiologic action of TRH is to regulate the set-point fo r negative feedback, a sudden drop in plasma thyroid hormone concentra tion should stimulate the same rate of in vivo increase in TSH secreti on from normal and TRH-deprived thyrotrophs. To test this hypothesis, 3 experiments were performed in which young adult female rats were div ided into 3 groups of 6-10 rats each: intact controls, hypothalamic pa raventricular nuclei ablation (PVN) and sham-ablated (Sham). Sham and PVN rats were thyroparathyroidectomized 2-4 weeks after brain lesions and serial blood samples taken in all groups at frequent intervals fro m 0 to 58 days post-thyroidectomy. Plasma TSH was significantly higher than in intact controls by 3 days post-thyroidectomy in both the Sham and PVN groups (p < 0.05). At 14 days PVN plasma TSH was 4 x higher a nd at 30 days 8 x higher than in intact controls and remained consiste ntly at 50% of that of the Sham group. There was no statistical differ ence between PVN and Sham in the rate of increase in TSH. Plasma T4 wa s 40% lower in PVN than in Sham at the time of thyroidectomy and becam e undetectable in both by day 3. The prompt parallel rate of rise of p lasma TSH in Sham and PVN groups following thyroidectomy indicates tha t a primary physiologic action of TRH in the thyrotroph is to control the set-point for thyroid hormone negative feedback on TSH secretion. However, this does not appear to be the sole mechanism by which TRH in fluences TSH secretion since even by 2 months post-thyroidectomy, when plasma TSH concentration had plateaued, plasma TSH was 50% lower in P VN than in Sham rats.