Search for fat-soluble ligand of nuclear orphan receptor.

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Steroid/thyroid/vitamin A,D nuclear receptors form a gene superfamily, and they resemble each other in terms of structure and function. Besides of the nuclear receptors, whose ligands have been found, receptors with unknown ligands exist as "orphan receptor" . When the ligand for orphan receptor will be identified, a new signaling pathway becomes clear. Moreover, a cross-talk with the signaling pathways for fat-soluble ligands will be clarified.In the present study, the subtypes and isoforms for vitamin A receptors (RARs, RXRs) and vitamin D receptors (VDR) as well as orphan receptors have been searched with cDNAs encoding RAR,RXR and VDR from the cDNA libraries of various mammalian tissues. Consequently, we found a VDR isoform (VDR1) acting as a dominant negative receptor against the wild type of VDR (VDR0). Considering the presence of multiple active forms of vitamin D on biological actions, one of these compounds may act as a ligand for VDR1. In addition, the functional analysis of identified orphan receptors is under investigation.