Decreased Outer Ring Monodeiodination of Thyroxine and Reverse Triiodothyronine in the Fetal and Neonatal Rat*

Abstract

Studies of the deiodination of T4 and rT3 were carried out in the perinatal rat. As compared to the adult male, the in vitro hepatic homogenate conversion of T4 to T3 was strikingly reduced in the 14 and 19 day-old fetal rat, increased progressively after birth, and reached adult male values by day 5. T4 or T3 administration enhanced and starvation decreased in vitro hepatic T3 generation from T4 in the neonatal rat. A highly significant decrease in in vitro degradation of [l25I]rT3 was also observed in the perinatal rat and adult values were reached by day 5. In vivo disposal of iv administered [125I]rT3 was studied in perinatal rats. Ten minutes after iv [125I]r3, the percentage of total 125I- remaining in the serum as [125I]r3 in the 20-day-old fetal rat was 70% and decreased progressivel towards adult values throughout the neonatal period. The metabolic clearance rate of rT3 was much slower in the 10-day-old neonate as compared to the adult rat (1.4 ml/min-100 g vs. 6.7). In comparison to adult values, 19-day-old fetal serum T4 was decreased, serum T3 was undetectable, and serum rT4 was markedly increased (75 ±1.5 ng/dl vs. undetectable rT3 in the adult). Amniotic fluid rT3 concentration at 19 days gestation was 63 ± 8 ng/dl. Serum rT3 concentration declined progressively during early neonatal life and became essentially undetectable by day 7 (6 ng/dl), while serum T4 and T3 concentrations increased progressively, reaching adult values within the second and third week, respectively. These studies suggest that decreased T4 and rT3 outer ring monodeiodination contributes to the increased serum rT3 and decreased serum T3 concentrations observed in the fetal and neonatal rat. In view of the low serum T4 substrate in the perinatal rat, preferential inner ring monodeiodination of T4 to rT3 may also occur.