Acephate interferes with androgen synthesis in rat immature Leydig cells.
Acephate interferes with androgen synthesis in rat immature Leydig cells.
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DOI：
10.1016/j.chemosphere.2019.125597
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发表时间：
2019-12
期刊：
影响因子：
8.8
通讯作者：
Yiyan Wang;Yao-yao Dong;Siwen Wu;Qiqi Zhu;Xiaoheng Li;Shiwen Liu;T. Huang;Huitao Li;R. Ge
中科院分区：
文献类型：
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作者：
Yiyan Wang;Yao-yao Dong;Siwen Wu;Qiqi Zhu;Xiaoheng Li;Shiwen Liu;T. Huang;Huitao Li;R. Ge
乙酰甲胺磷是一种有机磷农药。它被广泛使用。然而，它是否抑制雄激素的合成和代谢仍不清楚。在本研究中，我们研究了乙酰甲胺磷对雄激素合成和代谢途径的抑制大鼠未成熟Leydig细胞培养3小时后的影响。乙酰甲胺磷以剂量依赖性方式抑制基础雄激素输出，抑制作用从0.5 μM开始。在50 μM浓度下，它显著抑制促黄体生成素和8-Br-cAMP刺激的雄激素分泌。在50 μM浓度下，它显著抑制孕酮介导的雄激素输出。乙酰甲胺磷在≥ 0.5 μM、5 μM和50 μM时分别下调Hsd 3b 1及其蛋白的表达。乙酰甲胺磷在50 μM时直接阻断大鼠睾丸HSD 3B 1活性。乙酰甲胺磷不影响其他雄激素合成和代谢酶的活性，以及ROS的产生，增殖和凋亡的未成熟Leydig细胞。总之，乙酰甲胺磷靶向LHCGR、星星和HSD 3B 1，从而阻断大鼠未成熟Leydig细胞中的雄激素合成，而HSD 3B 1是乙酰甲胺磷最敏感的靶点。
Acephate is an organophosphate pesticide. It is widely used. However, whether it inhibits androgen synthesis and metabolism remains unclear. In the current study, we investigated the effect of acephate on the inhibition of androgen synthetic and metabolic pathways in rat immature Leydig cells after 3-h culture. Acephate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.5 μM. It significantly inhibited luteinizing hormone and 8-Br-cAMP stimulated androgen output at 50 μM. It significantly inhibited progesterone-mediated androgen output at 50 μM. Further study demonstrated that acephate down-regulated the expression ofHsd3b1and its protein at ≥ 0.5 μM,Lhcgrat 5 μM andStarat 50 μM. Acephate directly blocked rat testicular HSD3B1 activity at 50 μM. Acephate did not affect other androgen synthetic and metabolic enzyme activities as well as ROS production, proliferation, and apoptosis of immature Leydig cells. In conclusion, acephate targets LHCGR, STAR, and HSD3B1, thus blocking androgen synthesis in rat immature Leydig cells and HSD3B1 is being the most sensitive target of acephate.