Stimulation of testosterone synthesis by D-amino acid in testis Leydig cells

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D-Aspartate (D-Asp) increases human chorionic gonadotropin (hCG)-induced testosterone production in purified rat Leydig cells. Testosterone production was enhanced only in cells cultured with D-Asp for more than 3 h. The increased production of testosterone was well correlated with the amounts of D-Asp incorporated into the Leydig cells, and L-cysteine sulfinic acid, an inhibitor of D-Asp uptake, suppressed both testosterone production and intracellular D-Asp levels. D-Asp, therefore, is presumably taken up into cells to increase steroidogenesis. Intracellular D-Asp probably acts on cholesterol translocation into the inner mitochondrial membrane, the rate-limiting process in steroidogenesis. D-Asp enhances steady-state cellular mRNA and protein levels of Steroidogenic Acute Regulatory protein, which is a key regulatory factor in gonadal and adrenal steroidogenesis to increase the rate-limiting process. D-Asp therefore appears to increase testosterone production in rat Leydig cells by stimulating Steroidogenic Acute Regulatory protein gene expression. To our knowledge, this is the first report demonstrating a direct effect of D-Asp on gene expression in mammalian cells.