The critical role of thyroid hormones (TH) in normal human growth and fetal development is well recognised. The availability of tri-iodothyronine (T3) to bind to thyroid hormone receptors is determined by the local concentrations of T3, as well as the local action of deiodinase enzymes that determine conversion of T4.
Quantitative real time RT-PCR was used to quantify the expression of mRNAs encoding the specific deiodinase subtypes (D1, D2 & D3) in human fetal heart, liver and kidney from 1st and 2nd trimester pregnancies. 67 human fetuses were examined after surgical termination of pregnancy. These were compared with adult tissues (n=13). Western immunoblotting (WIB) was performed to examine protein expression in these tissues.
RT-PCR revealed the presence of D3 mRNA only in the fetal and adult heart (ventricular myocardium). D3 mRNA was significantly lower (compared to adults) at all gestational ages (8-12 wk. [0.03 fold; P<0.01], 13-17 wk. [0.1 fold, P<0.05] and 18-20 wks [0.05 fold, P<0.01]). In the fetal myocardium (1st and 2nd trimester samples), WIB demonstrated the presence of D3 protein only.
Fetal liver expressed D1, D2 and D3 mRNAs from 18-20 wk. Only D2 mRNA was elevated in early pregnancy (8-16 wk. [zenith of 8.3 fold, P<0.05]), whilst D1 mRNA was reduced compared to adult samples. In fetal 1st trimester liver samples, WIB demonstrated the presence of D2 and D3 protein only.
In fetal kidney increased D3 mRNA expression was noted compared with adult (8-12 wk. [2.5 fold, P<0.01], at 13-17 wk. [4-fold, P<0.001] and at 18-20 wk. [3.1 fold, P<0.01]). Conversely, D1 and D2 mRNAs were significantly lower in all gestations of fetal life (all 0.03-fold, P<0.01) compared with adults. In fetal kidney only D3 protein was identified using WIB.
These data support the view that local actions of deiodinases provide a critical role in ligand supply to TH receptors and hence T3 action in developing tissues.
08 - 11 Apr 2002
British Endocrine Societies