Comparison of lodothyronine 5'-Deiodinase and Other Thyroid-Hormone-dependent Enzyme Activities in the Cerebral Cortex of Hypothyroid Neonatal Rat EVIDENCE FOR ADAPTATION TO HYPOTHYROIDISM

adult rat cerebral cortex (Cx) derives from 5'-deio-dination of thyroxine (T4) within this tissue. The ac-tivity of iodothyronine 5'-deiodinase (I 5'D), the en-zyme catalyzing T4 to T3 conversion, increases rapidly after thyroidectomy, suggesting that this could be a compensatory response to hypothyroxinemia. To eval-uate this possibility during the period of central ner-vous system maturation, we studied several thyroid hormone-responsive enzymes (aspartic transaminase [AT], succinic dehydrogenase [S.D.], and Na/K ATPase) in the Cx of 2-, 3-, and 4-wk-old rats. The rats were made congenitally hypothyroid by placing 1, 2, 5, and 20 mg methimazole (MMI) in 100 ml of the mothers' drinking water from day 16 of gestation throughout the nursing period and to the litters after weaning. In addition, serum thyroid hormones, I 5'D, and, in some experiments, in vivo T4 to T3 conversion in Cx were measured in the same pups. Serum T4 concentrations varied from <1 to 40 ng/ml and were generally in-versely related to maternal MMI dose. Serum T3 was less affected by MMI than was T4. At 2 wk, decreases in AT, S.D., and ATPase were present in the 20-mg-MMI group but not in the 5-mg-MMI pups despite low serum T4 (<10 ng/ml) in the latter. At 3 and 4 wk, both 5- and 20-mg-MMI groups had significant re-ductions in these cortical enzymes despite a normal serum T3 in the 5-mg-MMI rats. Cortical I 5'D activity was 10-fold the control value in 5- and 20-mg-MMI Address all correspondence to Dr. Silva, Thyroid Diag