Liu M Y, Lai H Y, Yang B C, Tsai M L, Yang H Y, Huang B M
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Life Sci. 2001 Jan 12;68(8):849-59. doi: 10.1016/s0024-3205(00)00983-8.
Lead is an environmental and occupational pollutant. It has been reported that lead affects the male reproductive system in humans and animals. However, the cellular mechanism of the adverse effect of lead on Leydig cell steroidogenesis remains unknown. To clarify whether lead has a direct effect on Leydig cells and how lead affects Leydig cells, MA-10 cells, a mouse Leydig tumor cell line, were exploited in this study. Lead acetate significantly inhibited hCG- and dbcAMP-stimulated progesterone production in MA-10 cells at 2 h. Steroid production stimulated by hCG or dbcAMP were reduced by lead. The mechanism of lead in reducing MA-10 cell steroidogenesis was further investigated. The expression of Steroidogenic Acute Regulatory (StAR) protein and the activities of P450 side-chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzymes were detected. Cells were treated with dbcAMP, 22R-hydroxycholesterol or pregnenolone alone or in combination with lead acetate ranging from 10(-8) to 10(-5) M for 2 h. The expression of StAR protein stimulated by dbcAMP was suppressed by lead at about 50%. Progesterone productions treated with 22R-hydroxycholesterol or pregnenolone were reduced 30-40% in lead-treated MA-10 cells. These data suggest that lead directly inhibited steroidogenesis by decreasing StAR protein expression and the activities of P450scc and 3beta-HSD enzymes with a dose-response trend in MA-10 cells. Moreover, cadmium, a calcium channel blocker, abolished inhibitory effect of lead on MA-10 cell steroid production. This indicates that lead might act on calcium channel to regulate MA-10 cell steroidogenesis.
铅是一种环境和职业污染物。据报道，铅会影响人类和动物的雄性生殖系统。然而，铅对睾丸间质细胞类固醇生成产生不良影响的细胞机制尚不清楚。为了阐明铅是否对睾丸间质细胞有直接影响以及铅如何影响睾丸间质细胞，本研究采用了小鼠睾丸间质细胞瘤细胞系MA - 10细胞。醋酸铅在2小时时显著抑制MA - 10细胞中hCG和dbcAMP刺激的孕酮生成。铅降低了hCG或dbcAMP刺激的类固醇生成。进一步研究了铅降低MA - 10细胞类固醇生成的机制。检测了类固醇生成急性调节（StAR）蛋白的表达以及P450侧链裂解酶（P450scc）和3β - 羟基类固醇脱氢酶（3β - HSD）的活性。细胞分别单独用dbcAMP、22R - 羟基胆固醇或孕烯醇酮处理，或与浓度范围为10(-8)至10(-5) M的醋酸铅联合处理2小时。dbcAMP刺激的StAR蛋白表达被铅抑制了约50%。在铅处理的MA - 10细胞中，用22R - 羟基胆固醇或孕烯醇酮处理后的孕酮生成降低了30 - 40%。这些数据表明，铅通过降低StAR蛋白表达以及P450scc和3β - HSD酶的活性，在MA - 10细胞中以剂量反应趋势直接抑制类固醇生成。此外，钙通道阻滞剂镉消除了铅对MA - 10细胞类固醇生成的抑制作用。这表明铅可能作用于钙通道来调节MA - 10细胞的类固醇生成。
