Retinoid receptors belong

These retinoid receptors must form dimers before they interact with RAREs. RARs must form heterodimers with RXR.S, whereas RXRs may also form homodimers. It appears that the RAREs for the homodimers differ from those for the heterodimers. This implies that they may activate different sets of genes. RXRs also form hetcrodimers with thyroid hormone receptors and vitamin O receptois. increasing their affinity for DNA. Several enzymes whose expression depends on RXR have been found. The available experimental data provide convincing evidence that these proteins are, in fact, nuclear receptors belonging to the steroid/thyroid hormone superfamily. They mediate important aspects of vitamin A function. The existence of proteins that specifically bind retinoic acid substantiates the implication of retinoic acid as a physiological form of vitamin A. 

Retinoic X receptors (RXR, a, (3 and " (), also termed rexinoid receptors, are usually classified among orphan receptors, but belong to the thyroid/retinoid family. RXR is an obligatory partner dimerizing with other thyroid/retinoid receptors. RXR selectively bind the 9-cis isomer of retinoic acid, whereas RAR bind aU-tran retinoic acid as well as its 9-cis isomer. RXR selective agonists are termed rexi-noids, like bexarotene used as an antineoplastic in the treatment of cutaneous T-cell lymphoma and the cutaneous lesions of T-cell lymphomas and Kaposi s sarcoma. 

Bexarotene (Targretin) belongs to a subclass of retinoids that selectively bind to and activates retinoid X receptors (RXRs), which have biological properties distinct from those of RARs. In vitro, bexarotene exerts antiproliferative effects on some tumor lines of hematopoietic and squamous cell origin. 

Class II receptors are heterodimers. To this group belong receptors for non-steroidal compounds, such as the retinoids. The heterodimers are composed, for example, of a 9-m-retinoic-acid-bound monomer combined with an all-traw5-retinoic-acid-bound monomer or with a thyroid-hormone-bound monomer. These hetero-dimeric receptors bind to hexameric DNA repeats. 

It is assumed that some compounds of this group (AHTN and ATTN) may bind to the retinoid acid receptor (RAR) or retinoid X receptor (RXR) because their structure shows some similarity with synthetic RXR ligands [364,365]. The RAR and RXR belong to the steroid/thyroid hormone nuclear receptor super family. They play a central role in the regulation of many intracellular receptor pathways [366]. However, all these assumptions and predictions, especially the predicted high bioconcentration potential of the PMFs, have to be investigated experimentally. 

PPARs belong to a family of nuclear transcription factors that heterodimerize with retinoid X receptors (RXR) and function in a ligand-dependent manner [5]. They can activate transcription through binding peroxisome proliferator activated receptor response elements (direct repeat of AGGTCA spaced by one nucleotide). To date, three different PPAR isoforms a, 5/p, and y (and splice variants) have been identified that are encoded by separate genes. The tissue-specific expression pattern of these transcription factors is indicative of their function in those tissues [6]. 

The retinoic acids of retinoids could reveal widely their potential effects such as vertebrate development, cellular differentiation and vital homeostasis. A retinoic acid receptor RARal belonging to the superfamily of nuclear ligand-activated transcriptional regulators could regulate these receptors of steroid hormone, thyroid hormone, and vitamin D3. 

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