Dowling A L, Martz G U, Leonard J L, Zoeller R T
Biology Department, Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Neurosci. 2000 Mar 15;20(6):2255-65. doi: 10.1523/JNEUROSCI.20-06-02255.2000.
Despite clinical evidence that thyroid hormone is essential for brain development before birth, effects of thyroid hormone on the fetal brain have been largely unexplored. One mechanism of thyroid hormone action is regulation of gene expression, because thyroid hormone receptors (TRs) are ligand-activated transcription factors. We used differential display to identify genes affected by acute T(4) administration to the dam before the onset of fetal thyroid function. Eight of the 11 genes that we identified were selectively expressed in brain areas known to contain TRs, indicating that these genes were directly regulated by thyroid hormone. Using in situ hybridization, we confirmed that the cortical expression of both neuroendocrine-specific protein (NSP) and Oct-1 was affected by changes in maternal thyroid status. Additionally, we demonstrated that both NSP and Oct-1 were expressed in the adult brain and that their responsiveness to thyroid hormone was retained. These data are the first to identify thyroid hormone-responsive genes in the fetal brain.
尽管有临床证据表明甲状腺激素对出生前的大脑发育至关重要，但甲状腺激素对胎儿大脑的影响在很大程度上仍未得到探索。甲状腺激素作用的一种机制是基因表达调控，因为甲状腺激素受体（TRs）是配体激活的转录因子。我们使用差异显示技术来鉴定在胎儿甲状腺功能开始之前给母体急性注射T4所影响的基因。我们鉴定出的11个基因中有8个在已知含有TRs的脑区中选择性表达，这表明这些基因直接受甲状腺激素调控。通过原位杂交，我们证实神经内分泌特异性蛋白（NSP）和Oct-1的皮质表达受母体甲状腺状态变化的影响。此外，我们证明NSP和Oct-1在成人大脑中均有表达，并且它们对甲状腺激素的反应性得以保留。这些数据首次鉴定出胎儿大脑中的甲状腺激素反应性基因。
