Regulace genové exprese receptory thyroidních hormonů

Oltová, Jana

Hormones coordinate various processes in living organisms and their action is mediated either by cell membrane receptors or nuclear receptors. Thyroid hormones (THs) have prominent effects on the growth, development, and many aspects of metabolism, embryogenesis and early life. Their receptors (TRs) belong to the nuclear receptor superfamily, whose members function as ligand-activated transcription factors, and depending on the context, they can act both as activators or as inhibitors of transcription. Thyroid hormone receptors are encoded by two genes, TRα and TRβ, and by alternative splicing multiple isoforms are generated. The major form of TR binds to T3-response element as a heterodimer with retinoid X receptor (RXR). TRs are able to bind T3-response elements (TREs) independently of ligand occupancy. TREs contain two or more subsequent half-site sequences of AGGTCA, which are usually arranged as direct repeats with four nucleotide spacing (DR4). TH-responsive target genes are involved in a wide range of cellular pathways. Example of such gene is Disp3, which might link TH and cholesterol metabolism in certain cell types.

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