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首页> 外文期刊>Reproductive toxicology >Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro.
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Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro.

机译：邻苯二甲酸单乙基己酯对未成熟和成年大鼠Leydig细胞体外类固醇生成的抑制作用。

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Di-2-ethylhexyl (DEHP) phthalate, one of the phthalates most widely distributed in our general environment, causes reproductive toxicity that is attributable to the action of its primary metabolite, mono(2-ethylhexyl) phthalate (MEHP). Here, we have investigated the effects of MEHP on steroidogenesis by primary cultures of immature and adult rat Leydig cells. In both cases MEHP (250muM) was found to inhibit stimulation of androgen production evoked by human chorionic gonadotropin (hCG). This was associated with decreased expression of steroidogenic acute regulatory (StAR) protein and reduced transport of cholesterol into mitochondria but no detectable adverse effect on steroidogenic enzymes. Moreover, upon exposure to MEHP alone, 5alpha-reductase activity was decreased in immature, but not in adult Leydig cells. All together, our findings demonstrate that MEHP exerts suppressive effects on hCG-activated steroidogenesis in primary cultures of immature and adult rat Leydig cells and suppresses 5alpha-reductase activity in immature and not of adult rat cells. This may partly explain the anti-androgenic effects of DEHP in vivo and indicate a higher susceptibility in younger subjects.
机译：邻苯二甲酸二-2-乙基己基（DEHP）邻苯二甲酸酯是我们一般环境中分布最广泛的邻苯二甲酸酯之一，其生殖毒性可归因于其主要代谢产物邻苯二甲酸单（2-乙基己基）邻苯二甲酸酯（MEHP）的作用。在这里，我们研究了未成熟和成年大鼠Leydig细胞的原代培养对MEHP对类固醇生成的影响。在这两种情况下，均发现MEHP（250μM）抑制人绒毛膜促性腺激素（hCG）引起的雄激素生成刺激。这与减少类固醇生成的急性调节（StAR）蛋白的表达和减少胆固醇向线粒体的运输有关，但对类固醇生成酶没有可检测到的不利影响。此外，仅暴露于MEHP时，未成熟的5α-还原酶活性降低，但成年Leydig细胞未降低。总之，我们的发现表明，MEHP在未成熟和成年大鼠Leydig细胞的原代培养物中对hCG激活的类固醇生成具有抑制作用，并在未成熟而非成年大鼠细胞中抑制5α-还原酶活性。这可能部分解释了DEHP在体内的抗雄激素作用，并表明在年轻受试者中敏感性更高。

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