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

D-氨基酸刺激睾丸 Leydig 细胞中的睾酮合成

• 批准号: 11672163
• 负责人: HOMMA Hiroshi
• 金额: $ 2.3万
• 依托单位: Kitasato University (2000)The University of Tokyo (1999)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672163/
• 关键词: D-Aspartate; testosterone; Steroidogenic acute regulatory protein; Leydig cells; steroidogenesis; glutamate transporter; human chorionic gonadotropin; テストテロン

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.

D-天冬氨酸（D-Asp）增加人绒毛膜促性腺激素（hCG）诱导的纯化大鼠Leydig细胞中睾酮的产生。只有在与D-Asp培养超过3 h的细胞中，才能提高Texyline的产量。睾酮的产生增加与D-Asp掺入Leydig细胞的量密切相关，而D-Asp摄取的抑制剂L-半胱氨酸亚磺酸抑制睾酮的产生和细胞内D-Asp水平。因此，推测D-Asp被细胞吸收以增加类固醇生成。细胞内D-Asp可能作用于胆固醇转运进入线粒体内膜，这是类固醇生成的限速过程。D-Asp增强类固醇生成急性调节蛋白的稳态细胞mRNA和蛋白水平，类固醇生成急性调节蛋白是性腺和肾上腺类固醇生成中增加限速过程的关键调节因子。因此，D-Asp似乎通过刺激类固醇生成急性调节蛋白基因表达来增加大鼠睾丸间质细胞中的睾酮产生。据我们所知，这是第一个报告表明，D-Asp对哺乳动物细胞中的基因表达的直接影响。

项目成果

Lee,J-A. et al.: "D-Aspartate localization in the rat pituitary gland and retina"Brain Res.. 838. 193-199

李，J-A。

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松本，M.

Hamase,K. et al.: "Alteration in the D-amino acid content of the rat pineal gland under anesthesia"Amino Acids. 17. 277-283 (1999)

哈马斯，K.