Acute changes in maternal thyroid hormone induce rapid and transient changes in gene expression in fetal rat brain.
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.
Dowling
A L
AL
Biology Department, Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Martz
G U
GU
Leonard
J L
JL
Zoeller
R T
RT
D000367:Age Factors; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D002540:Cerebral Cortex / Q000737:chemistry / Q000196:embryology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051863:Host Cell Factor C1; D017403:In Situ Hybridization; D008431:Maternal-Fetal Exchange; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics; D050811:Octamer Transcription Factor-1; D010446:Peptide Fragments / Q000235:genetics; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics
D004268:DNA-Binding Proteins; D051863:Host Cell Factor C1; D009419:Nerve Tissue Proteins; D050811:Octamer Transcription Factor-1; D010446:Peptide Fragments; C494168:Pou2f1 protein, rat; D012333:RNA, Messenger; C489913:Rtn1 protein, rat; D014157:Transcription Factors; D013974:Thyroxine