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The Journal of Neuroscience, March 15, 2000, 20(6):2255-2265
Acute Changes in Maternal Thyroid Hormone Induce Rapid and Transient Changes in Gene Expression in Fetal Rat Brain
Amy L. S. Dowling1, Gabriel U. Martz1, Jack L. Leonard2, and R. Thomas Zoeller1 1 Biology Department and Molecular and Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts 01003, and 2 Molecular Endocrinology Laboratory, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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 T4 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.
Key words: thyroid hormone; neuroendocrine-specific protein; NSP; Oct-1; POU-domain; cerebral cortex; brain development; differential display; congenital hypothyroidism
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062255-11$05.00/0
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