Prenatal ethanol exposure selectively reduces the mRNA encoding alpha-1 thyroid hormone receptor in fetal rat brain.
Some of the developmental defects characteristic of congenital or experimental hypothyroidism are also observed in children or experimental animals prenatally exposed to ethanol, suggesting that a subset of neurological defects attributable to ethanol exposure are produced by interfering with thyroid hormone action. In this article, we tested whether an ethanol treatment regimen known to produce neurological damage in rats can alter the expression of the mRNAs encoding the thyroid hormone receptor isoforms (TR alpha-1, TR alpha-2, and TR beta-1) in the fetal rat brain neocortex and hippocampus. Rats were fed an ethanol-containing diet beginning on gestational day (G) 6 and continuing until sacrifice on G15, G17, or G21; controls included animals pair-fed a liquid control diet or fed lab chow. Ethanol selectively reduced the expression of TR alpha-1 mRNA in the neocortex and hippocampus on G21, compared with pair-fed and control fetuses. In contrast, pair-feeding selectively reduced TR alpha-2 mRNA in both neocortex and hippocampus on G21, and increased TR beta-1 mRNA on G17. These data support the hypothesis that ethanol may interfere with thyroid hormone action during fetal brain development. In addition, these data indicate that ethanol and pair-feeding exert independent effects on thyroid hormone receptor expression in the developing brain.
Scott
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Department of Pathology, University of Missouri School of Medicine, Columbia, USA.
Sun
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Zoeller
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RT
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D020318:Rats, Long-Evans; D011988:Receptors, Thyroid Hormone / Q000235:genetics*
D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone