Thyroid Hormone Receptor Gene Expression in First Trimester Human Fetal Brain

Abstract

Maternal thyroid hormone is transferred to the fetus early in pregnancy and is postulated to regulate brain development. Thyroid hormone nuclear receptor (TR) proteins are present in fetal brain, but their isoformal composition is unknown. We therefore investigated the ontogeny of TR isoforms and related splice variants in first trimester human fetal brain (n = 9) by semi-quantitative reverse transcriptase-polymerase chain reaction analysis. Expression of the TRβ1, TRα1 and c-erbAα2 isoforms was detected from 8.1 weeks gestation (wg). An additional truncated species was detected with the c-erbAα2 primer set, consistent with the c-erbAα3 splice variant previously described in the rat. All c-erbAα-derived transcripts were co-ordinately expressed and increased (ca.8-fold) between 8.1 and 13.9 wg. A more complex ontogenic pattern was observed for TRβ1, suggestive of a nadir between 8.4 and 12.0 wg. These findings point to an important role for the TRα1 isoform in mediating maternal thyroid hormone action during first trimester human fetal brain development.