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

Abstract

Placental deiodination of T4 to rT3 has been proposed as the factor controlling materno-fetal transmission of T4. We investigated T4 transfer in the isolated perfused human placental lobule with and without addition of the deiodinase inhibitor, iopanoic acid. T4 (150 nmol/L) in protein-free medium was added to the maternal circuit. Without iopanoic acid, the appearance of T4 in the fetal circuit was very low, with fetal T4 levels reaching only 4.1 +/- 0.84 pmol/L at 6 h. Levels of rT3 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 T3 could be measured in either circuit. Addition of 0.5 nmol/L iopanoic acid to maternal perfusate, however, resulted in significant reduction in the appearance of rT3 [maternal levels, 0.58 +/- 0.06 nmol/L (2% of control values); fetal levels, 0.33 +/- 0.03 nmol/L (2.7% of control values)] and a major (approximately 2700-fold) increase in T4 appearance in the fetal circuit, with fetal T4 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 T4.

The role of the placenta in thyroid hormone delivery to the fetus

“…47 With inhibition of D3 activity, a 2,700-fold increase was observed in the T 4 concentration within the fetal circuit. Placental D3 activity has also been postulated to contribute to the release of iodide ions into the fetal circulation, which are then used for thyroid hormone synthesis by the fetal thyroid gland.…”

Human selenoproteins at a glance

“…However, persistently high levels of DIO3 and low levels of T3 may have deleterious effects upon central nervous system development and brain function [157]. Thus, this expression pattern may refl ect the organism's attempt to protect the fetal central nervous system from inappropriate levels of T4 and T3 [159]. DIO3 is induced with increasing T4 levels and, like DIO2, almost insensitive towards PTU and gold(I).…”

Biochemical Mechanisms of Thyroid Hormone Deiodination

“…Compared to the adult, plasma T 3 concentrations are very low in the fetus, whereas levels of rT 3 are more than 10-fold higher than in the adult (52). This fetal profile has been explained by the high D3 activities in the placenta, which limits transplacental passage of maternal T 4 and T 3 to the fetus by converting T 4 to rT 3 and T 3 to 3,3Ј-T 2 during placental transfer (53,54).…”