LONG-LASTING EFFECTS OF TRIAC AND THYROXINE ON THE CONTROL OF THYROTROPIN AND HEPATIC DEIODINASE TYPE-I

The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For thi s purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T-4) and a short-acting one , triiodothyroacetic acid (Triac). Based on preliminary experiments wi th different doses of T-4 and Triac, hypothyroid rats (N=84) received over 6 days' injections of 10 nmol Triac or 2 nmol T-4/100 g body wt p er day. Biological effects of Triac and T-4 were measured in the pitui tary, liver and kidney up to 8 days after stopping treatment, With Tri ac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9+/-1.8 mu g/l (hypothyroid 14. 5+/-0.8 mu g/l). The rapid changes in serum TSH levels were followed b y a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to; that after T-4 in jection. Even 8 days after Triac treatment, serum TSH levels did not r each the hypothyroid control levels, Changes in beta-TSH mRNA levels a lso showed a prolonged inhibition after both treatments and a slow ret urn to hypothyroid values, which was not complete 8 days after stoppin g 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 T-4. Again, t he 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 r apid 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 T-4 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 ef fects vary markedly, not only. from organ to organ (TSH/5'D-I) but als o within the same organ, depending on the parameters (5'D-I/spot 14).