Signaling by Retinoids, Vitamin D3, and the T3-Hormone

There has also been a report of activation of the estrogen receptor mediated by the neurotransmitter dopamine (Power et al., 1991). This mechanism of activation is independent of that by the hormone. 

Ligands of the RXR-heterodimer group and the orphan receptors are chemically more diverse than the ligands of the steroid family. Representative hgands of this group are the retinoids all-trans retinoic acid, 9-cis retinoic acid, the T3 hormone and vitamin D3 (fig. 4.1). 

In contrast to signal transduction by the steroid hormone receptors there are multiple pathways by which the ligands of this group are made available for receptor activation (fig. 4.11)  

A further, more dramatic difference to the steroid hormone receptors is the localization of the receptors. The receptors for the retinoids (RAR and RXR, see table 4.1), the T3 hormone (T3R) and vitamin D3 (VDR) are mainly localized in the nucleus and their activity is not controlled by the heat shock proteins. The receptors also bind the corresponding HRE in the absence of hormone, in which case they can then act as repressors of gene activity. In the presence of the hormone an activation of gene expression is usually observed. 

Initial studies on the receptors of all-trans retinoic acid, vitamin D3 and the T3-hor-mone assumed that these receptors boimd their HRE s in homodimeric form. It became clear with the discovery of the receptors for 9-cis retinoic acid that this simple 

Details of the activation and transport into the nucleus remain unknown. Additional proteins like RAP46 have been identified that function in cooperation with the chaperones and participate in nuclear transport and also activation of the receptor. After dissociation of the heat shock proteins, the hormone-receptor complex is capable of specific binding on the HRE and of transactivation. 

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