Steroid/thyroid hormones, vitamin A and vitamin D act as a ligand for nuclear receptors, all of which belong to a gene superfamily and are ligand-inducible transcription factors. Most of actions of these ligands is exerted by the nuclear receptor-mediated gene expression. The target enhancer elements referred as hormone response elements are composed of two core hexmer motifs. Homo- and heterodimers of non-steroid hormone receptors bind direct repeated elements, and homodimers of steroid receptors bind inverted repeats. Heterodimer of Fos and Jun, the other transcription factors, is activated as AP1 activity in response to inflammation. In agreement with in vivo observation that vitamin A (retinoid) and glucocorticoid show anti-inflammatory activities, the AP1 activity is inhibited in a liganddependent way by these nuclear receptors upon the DNA binding sites for AP1.
Moreover, we found that the gene expression of platelet-activating factor receptor (PAFR) is regulated by thyroid hormone and vitamin A in intact animal. Functional analysis of two promoters of this gene revealed that the response elements are located in the one of two promoters. Thus, the actions of PAF may be modified by the status of these ligands through the levels of PAFR.
