Effects of graded doses of triiodothyronine on TSH synthesis and secretion rates in hypothyroid rats.

Abstract

Abstract. The effects of a graded low dose of T3 on plasma TSH, anterior pituitary TSH content (AP-TSH) and on TSH synthesis and secretion rates, were studied in adult male rats previously treated for 7 days with 0.01% prophylthiouracil (PTU). Pituitary TSH content, plasma T3, T4 and TSH levels were measured by RIA at 0, 6, 12, 24 h after the injection of T3 ranging from 0.1 to 0.75 μg/100 g b.w. Saline treated normal rats served as control. The 7-day PTU treated rats displayed low but still detectable thyroid hormone plasma levels; high plasma TSH levels were observed, but with no further increase after TRH injection as the AP-TSH content was depleted. Injections of T3 increased plasma T3 in proportion with the dose given. Plasma T4 remained low and there was no significant decrease in plasma TSH until doses of 0.2 μg/100 g b.w. T3 was given. Then the transient TSH depression was dose-dependent from 0.2 to 0.75 μg/100 g b.w. The AP-TSH content increased regularly from 0.2 μg/T3 onwards, overlapping the transient inhibition of TSH secretion resulting in a 3-fold increase in the AP-TSH content, suggesting a positive action of T3 on TSH synthesis. In addition, TSH response to TRH was observed at every time studied after T3 injection. Then, the different groups were injected with [125I]rTSH in order to estimate metabolic clearance rates, TSH secretion and synthesis rates. The half-life of [125I]rTSH (22 min) and its metabolism clearance rates (16 ± 0.4 ml/h/100 g b.w.) were found similar in all groups. Whereas the TSH secretion rates was highly reduced in the normal rats receiving 0.3 μg T3 (156 ± 9 vs 408 ± 22 μg/24 h in normal rats), the PTU group displayed a 3-fold increased secretion rate (1222 ± 44 μg/24 h) which was not modified by the injection of 0.1–0.2 μg T3 and decreased to 868 and 472 μg/24 h with 0.3 μg and 0.75 μg T3, respectively. TSH synthesis rates were found highly increased in the PTU group (1222 ± 44 μg/d vs 408 ± 22 μg/d in normal rats) and was neither increased nor reduced in the 7-day PTU rats receiving 0.1–0.3 μg T3 but a slight reduction was observed only in the 0.75 μg T3 group. These data show that 0.1–0.2 μg/100 g b.w. T3 changed neither TSH secretion nor its synthesis rates while 0.3 μg more or less a replacement dose inhibited TSH secretion without changing TSH synthesis rates, resulting in a AP-TSH replenishment. Therefore, no direct positive effect of low doses of T3 on TSH synthesis could be demonstrated over 24 h while higher doses are capable of inhibiting first secretion and then synthesis of TSH.