The role of the deiodinases D1, D2, and D3 in the tissue-specific and 
time-dependent regulation of thyroid hormone bioactivity during fetal 
development has been investigated in animals but little is known about the 
ontogeny of these enzymes in humans. We analyzed D1, D2, and D3 activities in 
liver microsomes from 10 fetuses of 15-20 weeks gestation and from 8 apparently 
healthy adult tissue transplant donors, and in liver homogenates from 2 fetuses 
(20 weeks gestation), 5 preterm infants (27-32 weeks gestation), and 13 term 
infants who survived up to 39 weeks postnatally. D1 activity was determined 
using 1 microM [3',5'-125I]rT3 as substrate and 10 mM dithiothreitol (DTT) as 
cofactor, D2 activity using 1 nM [3',5'-125I]T4 and 25 mM DTT in the presence of 
1 mM 6-propyl-2-thiouracil (to block D1 activity) and 1 microM T3 (to block D3 
activity), and D3 activity using 10 nM [3,5-125I]T3 and 50 mM DTT, by 
quantitation of the release of 125I. The assays were validated by high 
performance liquid chromatography of the products, and kinetic analysis 
[Michaelis-Menten constant (Km) of rT3 for D1: 0.5 microM; Km of T3 for D3: 2 
nM]. In liver homogenates, D1 activity was not correlated with age, whereas D3 
activity showed a strong negative correlation with age (r -0.84), with high D3 
activities in preterm infants and (except in 1 infant of 35 weeks) absent D3 
activity in full-term infants. In microsomes, D1 activities amounted to 4.3-60 
pmol/min/mg protein in fetal livers and to 170-313 pmol/min/mg protein in adult 
livers, whereas microsomal D3 activities were 0.15-1.45 pmol/min/mg protein in 
fetuses and <0.1 pmol/min/mg protein in all but one adult. In the latter sample, 
D3 activity amounted to 0.36 pmol/min/mg protein. D2 activity was negligible in 
both fetal and adult livers. These findings indicate high D1 and D3 activities 
in fetal human liver, and high D1 and mostly absent D3 activities in adult human 
liver. Therefore, the low serum T3 levels in the human fetus appear to be caused 
by high hepatic (and placental) D3 activity rather than caused by low hepatic D1 
activity. The occasional expression of D3 in adult human liver is intriguing and 
deserves further investigation.