Sequential changes in the pituitary thyroid axis after chronic TRH administration: effects on euthyroid and thyroxine...

The effect of chronic oral thyrotrophin-releasing hormone (TRH) administration on thyrotrophin (TSH), L-triiodothyronine (T3) and L-thyroxine (T4) serum levels, pituitary TSH concentration and serum response to acute TRH injection, has been studied in female rats under different thyroidal conditions: sham-operated control animals, and thyroidectomized animals receiving 25 micrograms L-T4/100 g body weight/day. After 30 days, these groups were divided into two subgroups (6-10 animals per group), one receiving the aforementioned treatment and the other the same plus 2 mg TRH/10 ml distilled water (DW), as drinking water. TRH-treated sham-operated animals showed significantly reduced serum and pituitary TSH levels and increased serum T3 levels at most of the times studied (1, 6, 10, 18 and 34 days of oral TRH or DW administration), and a transient elevation in serum T4 between day 1 and 6. Thyroidectomized-L-T4-treated animals showed increased serum and pituitary TSH levels throughout the treatment and reduced T3 and T4 serum levels at the beginning, as compared to thyroidectomized-L-T4-treated animals. TSH response to iv TRH administration on the 10th day of oral TRH administration was reduced in controls chronically treated with oral TRH as compared to non-treated controls, and was increased in thyroidectomized-L-T4-treated animals on chronic TRH vs the same group on oral DW. These results suggest that chronic TRH administration can stimulate TRH synthesis in vivo, bypassing the inhibitory effects of thyroid hormones, the increased pituitary TSH reserve being responsible for the partial restoration of a response to acute TRH injection in the thyroidectomized-L-T4-treated animals.