Maternal to fetal thyroxine transmission in the human term placenta is limited by inner ring deiodination

Placental deiodination of T-4 to rT(3) has been proposed as the factor controlling materno-fetal transmission of T-4. We investigated T-4 transfer in the isolated perfused human placental lobule with and without addition of the deiodinase inhibitor, iopanoic acid. T-4 (150 nnol/L) in protein-free medium was added to the maternal circuit. Without iopanoic acid, the appearance of T-4 in the fetal circuit was very low, with fetal T-4 levels reaching only 4.1 +/- 0.04 pmol/L at 6 h. Levels of rT, rose progressively in both circuits, reaching 28.8 +/- 5.5 nmol/L in the maternal and 12.4 +/- 3.2 nmol/L in the fetal circuit by 6 h. No T-3 could be measured in either circuit. Addition of 0.5 mmol/L iopanoic acid to maternal perfusate, however, resulted in significant reduction in the appearance of rT(3) [maternal levels, 0.58 +/- 0.06 nmol/L (2% of control values); fetal levels, 0.33 +/- 0.03 mmol/L (2.7% of control values)] and a major (similar to 2700-fold) increase in T-4 appearance in the fetal circuit, with fetal T-4 levels reaching 10.1 +/- 3.4 nmol/L at 6 h. These results support the hypothesis that placental inner ring (type III) deiodination is a major factor controlling placental transmission of maternal T-4.