Thyroid receptors

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

Marsh, G., Bergman, A., and Bladh, L.G. et al. (1998). Synthesis of p-hydroxybromodiphenyl ethers and binding to the thyroid receptor. Organohalogen Compounds 37, 305-308. 

Evans RM (1988) The steroid and thyroid receptor family. Science 240 889... 

Tsai MJ, O Malley BW (1994) Molecular mechanisms of action of steroid/thyroid receptor superfamiliy members. Annu Rev Biochem 63 451-486... 

As mentioned earlier, MeCP2 is not the only protein that associates with HD AC activities. Both MBD2 and MBDl repress transcription in histone deacetylation-dependent manner. Interestingly, MBD2 was found associated not only with class I histone deacetylases (HDACl and 2) from the Mi2/NuRD corepressor complex but also with class II histone deacetylases in the silencing mediator of retinoic and thyroid receptor (SMRT)/HDAC 5,7 complex [137]. 

Plasma estrogens in the blood and interstitial fluid are bound to SHBG, from which they dissociate to enter the cell and bind to their receptor. Two genes code for two estrogen receptor isoforms, and 3, which are members of the superfamily of steroid, sterol, retinoic acid, and thyroid receptors. The estrogen receptors are found predominantly in the nucleus bound to heat shock proteins that stabilize them (see Figure 39-4). 

Figure 17.3 The nuclear receptor superfamily. Steroid receptor family members and thyroid receptor family members differ in several structural and functional properties. The estrogen receptors share properties with both steroid and thyroid receptor families and are likely an evolutionary precursor to both families.

Table 17.2 DNA Recognition Sequences Utilized by Steroid, Estrogen, and Thyroid Receptor Family Members...

In contrast to the steroid receptor family, members of the thyroid receptor family typically do not associate with accessory proteins and are not localized to the extranucleus matrix. Rather, these receptors exist in the basal state associated with chromatin in the cell nucleus. When bound by hormone ligand, thyroid receptor family members dissociate from the chromatin and typically form heterodimeric combinations with the retinoid-X receptor (RXR). RXR also is capable of homodimerization in association with its ligand 9-cis retinoic acid. Thus high 9-cis retinoic acid levels apparently promote homodimerization, and low levels are permissive of heterodimerization of RXR with activation by the partner ligand. 

Synthroid Levothyroxine 25, 50, 75, 88, Tablet Hypothyroidism, Thyroid receptor Acacia, confectioner s sugar, Abbott Laboratories... 

Cheek AO, Kow K, Chen J, McLachlan JA (1999) Potential mechanisms of action of thyroid disruption in humans Interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin. Environ Health Perspect, 107(4) ... 

Thyroid receptor agonists consisting of thiazolidine-2,4-dione derivatives, (I), were prepared by Chiang (1) and used in the treatment of thyroid diseases including hypothyroidism and thyroid cancer. 

Phenyl naphthol derivatives, (V), prepared by Hangeland (5) were also effective as thyroid receptor agonists and used in treating hypothyroidism. 

ER Estrogen Receptor, AR Androgen Receptor, GR Glucocorticoid Receptor, TR Thyroid Receptor, RAR Retinoic Acid Receptor, RXR Retinoie X Receptor, PR Progesterone Receptor, VDR Vitamin D Receptor, PPAR Peroxisome Proliferator-Activated Receptor, PXR Pregnane X Receptor, ROR Retinoic Acid-Related Orphan Receptor, NHF-4 Hepatocyte Nuclear Eactor 4, ERR Estrogen-Related Receptor... 

II Thyroid receptor (TR) Heterodimer Tniodothyronine. thyroxin Direct repeat... 

Figure 6.18. Receptor site of thyroid receptor beta filled with spheres (for sake of clarity, sphere centers are depicted actual size of spheres is larger, so that spheres overlap) and thyronine. Crystal structure taken from the PDB (ID Ibsx).

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