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

D-天冬氨酸(D-Asp)可增加人绒毛膜促性腺激素(HCG)诱导的大鼠睾丸间质细胞睾酮的产生。D-Asp作用3h后，细胞内睾酮的生成才增加，睾酮的增加与D-Asp掺入间质细胞的量呈正相关，而D-Asp摄取的抑制剂L-半胱氨酸亚磺酸抑制了睾酮的生成和细胞内D-Asp的水平。因此，D-天冬氨酸可能被细胞吸收以促进类固醇的合成。细胞内D-天冬氨酸可能作用于胆固醇转运到线粒体膜内层，这是类固醇合成的限速过程。D-Asp可提高稳态细胞类固醇合成急性调节蛋白的mRNA和蛋白水平，这是性腺和肾上腺类固醇合成的关键调节因子，从而增加限速过程。因此，D-天冬氨酸似乎通过刺激类固醇生成急性调节蛋白基因的表达来增加大鼠睾丸间质细胞的睾酮产量。据我们所知，这是第一个证明D-Asp对哺乳动物细胞基因表达有直接影响的报告。

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.