Physiologic Significance of Epigenetic Regulation of Thyroid Hormone Target Gene Expression

European Thyroid Journal
João Anselmo, Carolina M Chaves

Abstract

In previous publications, we have reported our findings demonstrating that exposure to high maternal levels of thyroid hormones (TH) has life-long effects on the wild-type (WT, without THRB mutation) progeny of mothers with resistance to thyroid hormone beta (RTHβ). The mechanism of this epigenetic effect remains unclear. We reviewed the mechanisms involved in the epigenetic regulation of TH target genes and understand how they may explain the reduced sensitivity to TH in the WT progeny of RTHβ mothers. The availability of a large, formerly genotyped Azorean population with many individuals harboring the THRB mutation, R243Q, provided us a model to study the influence of fetal exposure to high maternal TH levels. The thyroid-stimulating hormone (TSH) response in WT adults was less suppressible following the administration of L-triiodothyronine (L-T<sub>3</sub>). This finding suggests reduced sensitivity to TH that is induced by an epigenetic mechanism resulting from exposure to high maternal levels of TH during pregnancy. The persistence of this effect across 3 generations of WT subjects favors transgenerational epigenetic inheritance. Based on preliminary studies in mice, we identified the naturally imprinted gene encoding dei...Continue Reading

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