Thyroid hormones are known to be important for optimal development of the human central nervous system. Classically, maternal thyroid hormones have not been thought to play a major role in defining central nervous system development. However, recent epidemiological evidence has indicated that subtle deficiencies in circulating maternal thyroid hormones in the first trimester of pregnancy are associated with adverse neurodevelopment.
We have used real-time PCR to quantitate the expression of mRNAs encoding the thyroid receptor isoforms (TRalpha1, alpha2, beta1 and beta2) and thyronine deiodinase subtypes (DI, DII and DIII) in human fetal cerebral cortex from the first and second trimesters of pregnancy. In addition, deiodinase subtype activities were also determined in these tissues and compared to 'normal' adult human cerebral cortex.
All iodothyronine deiodinase mRNAs (DI, DII and DIII) were expressed in human fetal cerebral cortex from 7 to 8 weeks of gestation. There was disparity in expression of deiodinase mRNAs and enzyme activities in these samples. Only TRalpha1 mRNA was more abundantly expressed in the fetal cerebral cortex than in adult tissues. In contrast, the TRalpha isoforms (alpha2 and beta1) were less significantly expressed than in adult tissues. There was little evidence that TRbeta2 was expressed in these tissues.
There is evidence that developing fetal brain as early as the first trimester expresses both TRs and exhibits the mechanisms of pre-receptor control of thyroid hormone supply.
08 - 11 Apr 2002
British Endocrine Societies