抄録
The brain weight is only 2% of the whole body weight, but it contains around 20% of the whole body cholesterol pool. Choresterol and its derivatives are identified to be the natural ligand for retinoic acid receptor-related orphan nuclear receptor (ROR)α, which is widely expressed in brain. Thus, RORα may control brain lipid metabolism, although its function in brain has not yet been fully understood. Apo AI is the major apolipoprotein in cerebrospinal fluid. Although Apo AI gene has native ROR response element (RORE), the role of RORα on Apo AI transcription in brain has not yet been clarified. Thus, we have investigated the effect of RORα and serum on Apo AI transcription. RORα mediated transcription on Apo AI RORE was activated with serum-contained medium, whereas such effect was not observed without serum, indicating that serum may contain a ligand for RORα. In addition to the role of RORα on this gene expression, it activates transcription through thyroid hormone (TH) receptor (TR), which is essential for normal brain development. Thus, we used a native TH response element, malic enzyme (ME) promotor, to examine the effect of RORα and found that TR action was augmented by RORα. Taken together, our results indicate that RORα contributes to sustain brain function in several ways; by lipid metabolism through RORE, and by augmenting TR-mediated transcription on TRE. [J Physiol Sci. 2008;58 Suppl:S137]
