Regulation of gene expression by D-amino acids

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We have reported that D-aspartate (D-Asp) increases human chorionic gonadotropin (hCG)-induced testosterone production in purified rat Laydig cells. D-Asp is presumed to be taken up into the cells and increases the protein and mRNA levels of Steroidogenic acute regulatory protein (StAR), which is an essential protein for the steroidogenesis. We found in this study that D-Asp increases StAR protein expression in mLTC-1 cells (mouse Leydig Tumor Cell-1), a cultured cell line that would be a suitable model of rat Leydig cells. In these cells, D-Asp promotes StAR protein expression only when the cells transiently express glutamate transporter, through which D-Asp is taken up into the cells. This result shows that D-Asp uptake is necessary for the stimulation of StAR gene expression. In addition, D-Asp stimulates StAR protein expression in the cells which stably express glutamate transporter, while it did not promote the protein expression in the parent mLTC-1 cells. These lines of evidence show that D-Asp should be taken up into mLTC-1 cells before it stimulates StAR gene expression. Details should be clarified on the mechanism of D-Asp stimulation of StAR gene expression in mLTC-1 cells.