Generation between Euthyroid and Hypothyroid Rats

Abstract. Propylthiouracil (PTU) in maximally inhibitory doses for liver and kidney iodothyronine 5'-deiodinase activity (5'D-I), reduces extrathyroidal T4 to T3 conversion by only 60-70 % in euthyroid rats. A second pathway of T4 to T3 conversion (5D-II) has been found in pituitary, central nervous system, and brown adipose tissue. 5D-II is insensitive to PTU and increases in hy-pothyroidism, whereas 5'D-I decreases in hypothyroid rats. Thyroxine (T4) and triiodothyronine (T3) kinetics were assessed in euthyroid and thyroidectomized rats by non-compartmental analysis after injecting ['25I]T4 and ['3'I]T3. Neither the volume of distribution nor the rate of fractional removal of plasma T4 was affected by the thyroid status, but the fractional removal rate of T3 was-50 % reduced in hypothyroid rats (P < 0.001). Fractional T4 to T3 conversion was 22 % in euthyroid and 26 % in hypothyroid rats. In euthyroid rats, sufficient PTU to inhibit liver and kidney 5D-I>90 % reduced serum [125I]T3 after ['25I]T4 (results given as percent dose per milliliter X 10-3 +SEM): 4 h, control 16±2 vs. PTU 4+1, P < 0.005, and 22 h, control 6.4±0.4 vs. PTU 3.6±0.7, P < 0.025. In thyroidectomized rats, the same dose of PTU also inhibited 51-I in liver and kidney, but had no effect on the generation of serum ['251]T3 from [1251]T4. Similarly, after 1 gg T4/100 g bw was given to thyroid-ectomized rats, serum T3 (radioimmunoassay) increased Dr. Leonard is the recipient of a New Investigator Award (AM-30309). Address all correspondence to Dr. Silva, Thyroid Diagnostic Center