Modulation of thyroid hormone nuclear receptor levels by l-triiodothyronine (T 3) in the rat pituitary

Abstract

The concentration of thyroid hormone nuclear receptors varies from one tissue to another, the anterior pituitary (AP) gland possessing the highest. Since 3,5,3',1-triiodothyronine (T 3) controls within a narrow range the secretion of TSH from the pituitary gland, this study was carried out to establish whether T 3 modulates its own pituitary nuclear receptors and if so, whether this modulation is correlated with the thyroidal status and TSH secretion. Salt-solubilized T 3 nuclear receptors were measured in the AP gland of thyroidectomized and intact adult male rats as well as in thyroidectomized rats treated with T 3. In intact male rats the maximum binding capacity of pituitary T 3 nuclear receptors (MBC-T 3nR), determined by Scatchard analysis, was 578 ± 45 fmoles T 3/mg protein or 27 ± 3 fmoles T3/AP (mean ±SEM, n = 19). 2 weeks after thyroidectomy there was a marked decrease in serum T 3 and T 4 concentrations as well as in the MBC-T 3nR (231 ± 26 fmoles T 3/mg protein or 9.3 ± 1.2 fmoles T 3/AP, n = 7) which was still observed 8 and 16 weeks after thyroidectomy. The affinity constant ( K a) of T 3 for its pituitary nuclear receptors was significantly greater in thyroidectomized rats than in intact rats (3.61 ± 0.70 vs. 1.09 ± 0.15 ×10 10 M −1, P < 0.001). To test whether treatment with T 3 would restore a normal MBC-T 3nR, 2-week thyroidectomized rats were injected with T 3 (0.5 μg/100 g b.w.) and killed 10 min, 1, 3,15 or 24 h after T 3 injection. 10 min after T 3 injection MBC-T 3nR was not altered but it returned to normal values 1 h after injection (441 ± 97 fmoles T 3/mg protein) and was maintained so for at least 3 h. 15 h after T 3 injection MBC-T 3nR was again decreased in spite of serum T 3 levels that were twice as high as in normal rats. In contrast, when T 3 was injected at the dose of 1.0 μg/100 g b.w. the MBC-T 3nR was maintained within the normal range as long as 24 h after the injection (428 ± 125 fmoles T 3/mg protein) with serum T 3 concentrations that were twice the normal levels (1.27 ± 0.06 vs. 0.67 ± 0.01 ng/ml). These results support the hypothesis that T 3 modulates the concentration of its own nuclear receptors in the rat pituitary gland. The absence of any effect of T 3 10 min after injection is suggestive of an effect of T 3 on the synthesis of its receptors rather than on an alteration of unoccupied receptors that would require T 3 for adequate configuration and detection. This modulation of pituitary T 3 receptors by T 3 may provide an additional mechanism of regulation of TSH secretion in thyroid insufficiency.