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Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I

Juge-Aubry CE, Morin 0, Pernin AT, Liang H, Phillipe J, Burger AG. Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I. Eur J Endocrinol 1995;132:751–8.

The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For this purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T₄) and a short-acting one, triiodothyroacetic acid (Triac). Based on preliminary experiments with different doses of T₄ and Triac, hypothyroid rats (N= 84) received over 6 days' injections of lOnmol Triac or 2 nmol T₄/100 g body wt per day. Biological effects of Triac and T₄ were measured in the pituitary, liver and kidney up to 8 days after stopping treatment. With Triac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9 ± 1.8 µ/l (hypothyroid 14.5 ± 0.8 µg/l). The rapid changes in serum TSH levels were followed by a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to that after T₄ injection. Even 8 days after Triac treatment, serum TSH levels did not reach the hypothyroid control levels. Changes in β-TSH mRNA levels also showed a prolonged inhibition after both treatments and a slow return to hypothyroid values, which was not complete 8 days after stopping treatment. A second parameter was hepatic 5'-deiodinase type I (5'D-I), The 6-day treatment with Triac had a markedly stronger effect on 5'D-I enzyme activity and mRNA levels than treatment with T₄. Again, the effect disappeared slowly because hepatic activity was still above control levels 8 days after treatment. The mRNA levels of spot 14 also were higher with Triac. However, 4 days after stopping treatment with both hormones, mRNA levels had returned to hypothyroid values. These data suggest that at the pituitary level one can distinguish between rapid and slower effects. For 5'D-I activity, however, the effects are longlasting and there is no apparent difference in the duration of the effects between Triac or T₄. They last much longer than the injected hormone. Our results show that even for parameters closely controlled by thyroid hormones, the expression and duration of thyroid hormone effects vary markedly, not only from organ to organ TSH/5'D-I but also within the same organ, depending on the parameters (5'D-I/ spot 14).

Cristiana E Juge-Aubry, Thyroid Unit, Hôpital Cantonal Universitaire, 1211 Geneva 14, Switzerland

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