Search for fat-soluble ligand of nuclear orphan receptor.

类固醇/甲状腺/维生素A，D核受体形成一个基因超家族，它们在结构和功能方面彼此相似。除了已发现配体的核受体外，还存在配体未知的孤儿受体。当孤儿受体的配体被鉴定出来时，一条新的信号通路就变得清晰起来。在本研究中，维生素A受体（RAR，RXR）和维生素D受体（VDR）以及孤儿受体的亚型和同种型已被搜索的cDNA编码RAR，RXR和VDR从各种哺乳动物组织的cDNA文库。因此，我们发现了VDR亚型（VDR 1）作为一个显性负性受体对野生型VDR（VDR 0）。考虑到维生素D的多种活性形式对生物学作用的存在，这些化合物之一可以作为VDR 1的配体。此外，已鉴定孤儿受体的功能分析正在研究中。

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.