Tissue-specific patterns of changes in 3,5,3 '-triiodo-L-thyronine concentrations in thyroidectomized rats infused with increasing doses of the hormone. Which are the regulatory mechanisms?

We have measured 3,5,3'triiodothyronine (T-3) in 12 tissues from thyroidect omized (Tx) rats infused with increasing doses of T-3, and related them to their corresponding plasma levels. Young adult Wistar rats were surgically Tx. After 4 weeks, the animals were infused with placebo or T-3 (0.25, 0.50 , 0.75, 1.00 or 2.00 mu g/100 g body weight/day). Placebo-infused intact ra ts served as euthyroid controls. Plasma and samples of cerebral cortex, cer ebellum, brown adipose tissue (BAT), pituitary, liver, heart, lung, kidney, spleen, skeletal muscle, ovary and adrenal were obtained after 12-13 days of infusion. We determined plasma T-3 and thyrotropin (TSH), and tissue T-3 and thyroxine (T-4), the latter being virtually undetectable. Results were compared with the relationships between tissue and plasma T-3 in Tx rats o n T-4 infusions. Most tissues presented changes which paralleled those in p lasma T-3, irrespective of its source (infusion of T-3, or generation from infused T-4). However, at similar plasma T-3 concentrations, cerebral corte x, cerebellum and BAT (containing type II 5' iodothyronine deiodinase (DII) activity), reached much lower T-3 levels in the T-3-infused Tx rats, than in Tx rats on T-4, and required elevated plasma T-3 levels for normal tissu e T-3. In these tissues, and in the pituitary, T-3 concentrations were alwa ys lower than expected from plasma T-3 levels. On the contrary, the lung an d ovary of the T-3-infused Tx rats contained more T-3 than expected from pl asma T-3. Unexpectedly, both the ovary and adrenal attained higher tissue T -3 concentrations in Tx rats on T-3 than on T-4 at comparable plasma T-3 le vels. In conclusion, the patterns of changes of the concentrations of T-3 a s a function of increasing plasma T-3 are not only tissue-specific when T-4 is provided, but also when circulating T-3 is the only source of this iodo thyronine. Further studies are needed to identify the mechanisms involved i n the regulation of tissue T-3 concentrations. (C) Societe francaise de bio chimie et biologie moleculaire / Elsevier, Paris.