Complexity of the Interaction between HRE, Receptor and Hormone

There is an altogether complex interaction between H RE, receptor and hormone in the group of receptors for retinoids, vitamin D3 and the T3-hormone. The complexity is determined by the following factors  

To what extent hetero- or homodimers are formed depends upon the concentration of the various receptors in the particular cell type. The receptor concentration can furthermore be regulated via the general mechanisms as described in Chapters 1 and 2, whereby regulation at the level of expression of the receptors is particularly important. 

Among the receptors for the retinoids (RAR and RXR), there are at least three subtypes characterized, known as RARa, / , and y (RXR a,fi and y). The various subtypes differ from each other mainly in their amino acid sequence and are encoded in each case by their own gene. Furthermore, one finds isoforms of some of the receptors created by alternative splicing of the primary transcript. Altogether, the repertoire of the various receptor variants is enormously increased through the existence of the subtypes and by alternatively spliced receptors. Because the individual variants differ in their ability to form hetero- and homodimers as well as in their ability to activate and bind ligands, this results in a great variety of functionally different receptors. 

The hormone concentration necessary for the binding and activation of a receptor dimer can be very different for the various dimers. The available hormone concentration in a particular cell type thus plays an important role in receptor activation. The effective intracellular concentration of a hormone is furthermore subject to a diverse regulation mechanism (see Section4.5). 

The picture sketched above for the function of the receptors of the retinoids and the Tr and vitamin D3-hormones is in many points still incomplete. The cooperation of the activated receptors with other transcription factors, their interactions with the transcription apparatus and the influence of chromatin structure are still poorly understood. 

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