Thyroid hormone receptor gene expression in first trimester human fetal brain

Maternal thyroid hormone is transferred to the fetus early in pregnancy and is postulated to regulate brain development. Thyroid hormone nuclear recep tor (TR) proteins are present in fetal brain, but their isoformal compositi on is unknown. We therefore investigated the ontogeny of TR isoforms and re lated splice variants in first trimester human fetal brain (n = 9) by semi- quantitative reverse transcriptase-polymerase chain reaction analysis. Expr ession of the TR beta 1, TR alpha 1 and c-erbA alpha 2 isoforms was detecte d from 8.1 weeks gestation (wg). An additional truncated species was detect ed with the c-erbA alpha 2 primer set, consistent with the c-erb alpha 3 sp lice variant previously described in the rat. All c-erA alpha-derived trans cripts were co-ordinately expressed and increased (ca. 8-fold) between 8.1 and 13.9 wg. A more complex ontogenic pattern was observed for TR beta 1, s uggestive of a nadir between 8.4 and 12.0 wg. These findings point to an im portant role for the TR alpha 1 isoform in mediating maternal thyroid hormo ne action during first trimester human fetal brain development.