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FIGURE 6-18 Mapping of the functional domains of the thyroid receptor isoform TR/3-1. [Modified with permission from Lazar, M.A. (1993). Thyroid hormone receptors: Multiple forms, multiple possibilities. Endocr. Rev. 14, 184-193.]

known to be biologically active in the regulation of gene transcription (see Figures 6-20 and 1-45). The usual heterodimer partner is either the RAR or RXR receptor isoform, but under some circumstances the thyroid receptor can also form a heterodimer with the receptor for la,25(OH)2D3 (VDR). In addition, the ligand-binding domains of these receptors can be either occupied or unoccupied, depending upon the levels of free hormones available. Thus, there is a wide array of receptor species (both with and without ligand) that are able to regulate the transcription of target genes.

The unliganded thyroid receptor is functionally active and can repress the transcription of genes activated by T3. T3 binding to the thyroid receptor also can either activate or repress gene transcription (see Table 6-5). It is not yet known with certainty which form of the thyroid receptor (monomer, homodimer, or heterodimer) participates in negative or positive regulation; this is an area of research under intense investigation.

C. Production of Biological Responses

As already emphasized, the thyroid hormones are able to mediate a wide array of biological responses in many tissues of the body; Table 6-4 enumerates many of these responses. Evidence indicates that most of these responses are the consequence of the action of

Primary amino acid sequence of rat a

thyroid receptor ligand binding domain

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