Iodothyronine levels in the human developing brain: major regulatory roles of iodothyronine deiodinases in different areas.
Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T(4), T(3), and rT(3) and in the activities of the types I, II, and III iodothyronine deiodinases (D1, D2, and D3) in different brain regions in normal fetuses (13-20 wk postmenstrual age) and premature infants (24-42 wk postmenstrual age). D1 activity was undetectable. The developmental changes in the concentrations of the iodothyronines and D2 and D3 activities showed spatial and temporal specificity but with divergence in the cerebral cortex and cerebellum. T(3) increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T(3). Considerable D2 activity was found in the cortex, which correlated positively with T(4) (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T(3) was very low and increased only after midgestation. Cerebellum D3 activities were the highest (64 fmol/min.mg) of the regions studied, decreasing after midgestation. Other regions with high D3 activities (midbrain, basal ganglia, brain stem, spinal cord, hippocampus) also had low T(3) until D3 started decreasing after midgestation. D3 was correlated with T(3) (r = -0.682) and rT(3)/T(3) (r = 0.812) and rT(3)/T(4) (r = 0.889). Our data support the hypothesis that T(3) is required by the human cerebral cortex before midgestation, when mother is the only source of T(4). D2 and D3 play important roles in the local bioavailability of T(3). T(3) is produced from T(4) by D2, and D3 protects brain regions from excessive T(3) until differentiation is required.
Kester
Monique H A
MH
Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Martinez de Mena
Raquel
R
Obregon
Maria Jesus
MJ
Marinkovic
Danijela
D
Howatson
Allan
A
Visser
Theo J
TJ
Hume
Robert
R
Morreale de Escobar
Gabriella
G
D001921:Brain / Q000196:embryology*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism*; D009994:Osmolar Concentration; D013974:Thyroxine / Q000378:metabolism*; D014018:Tissue Distribution; D014284:Triiodothyronine / Q000378:metabolism*; D014285:Triiodothyronine, Reverse / Q000378:metabolism*; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D013974:Thyroxine; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D000097564:Iodothyronine Deiodinase Type II; C117274:iodothyronine deiodinase type III