Iodothyronine Levels in the Human Developing Brain: Major Regulatory Roles of Iodothyronine Deiodinases in Different Areas

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Abstract

Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T4, T3, and rT3 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. T3 increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T3. Considerable D2 activity was found in the cortex, which correlated positively with T4 (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T3 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 T3 until D3 started decreasing after midgestation. D3 was correlated with T3 (r = −0.682) and rT3/T3 (r = 0.812) and rT3/T4 (r = 0.889).

Our data support the hypothesis that T3 is required by the human cerebral cortex before midgestation, when mother is the only source of T4. D2 and D3 play important roles in the local bioavailability of T3. T3 is produced from T4 by D2, and D3 protects brain regions from excessive T3 until differentiation is required.

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