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Abstract：
Trimethyltin (TMT) is widely used in industry and agriculture. The present study aims to clarify the effects of in vitro TMT exposure on androgen biosynthesis and metabolism in immature Leydig cells (ILCs), and to unveil the underlying mechanism. It was found that 1-10μM TMT decreased ILC androgen productions under basal conditions. TMT at 10μM decreased luteinizing hormone (LH) or 8-Br-cAMP (8BR)-stimulated androgen productions from ILCs. TMT at 10μM decreased 22R-hydroxycholesterol (22R) and androstenedione (D4)-mediated androgen productions from ILCs. TMT at 0.1-10μM down-regulated the mRNA or protein expression levels of STAR, CYP11A1, 17β-HSD3, or NR5A1. TMT at 10μM directly inhibited the enzyme activities of CYP11A1 and 17β-HSD3. In conclusion, the present study demonstrated that in vitro TMT exposure decreased ILC function of androgen production, via exerting negative effects on the mRNA/protein expression levels, or enzyme activities of STAR, CYP11A1, 17β-HSD3, or NR5A1.
摘要：
三甲基锡(TMT)广泛应用于工农业领域。本研究旨在阐明体外TMT暴露对未成熟睾丸间质细胞（ILC）雄激素生物合成和代谢的影响。并揭示潜在的机制。发现在基础条件下，1-10μM的TMT降低了ILC雄激素的产生。10μM的TMT降低了ILC中黄体生成素（LH）或8-Br-cAMP（8BR）刺激的雄激素产生。10μM的TMT降低了ILC中22R-羟基胆固醇（22R）和雄烯二酮（D4）介导的雄激素产生。TMT在0.1-10μM下调STAR的mRNA或蛋白表达水平，CYP11A1、17β-HSD3或NR5A1。10μM的TMT直接抑制CYP11A1和17β-HSD3的酶活性。总之,本研究表明，体外TMT暴露降低了ILC的雄激素产生功能，通过对mRNA/蛋白质表达水平产生负面影响，或STAR的酶活性，CYP11A1、17β-HSD3或NR5A1。
